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  • Khorana score and thromboembolic risk in stage II–III colorectal cancer patients: a post hoc analysis from the adjuvant TOSCA trial
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2020-01-20
    Sandro Barni; Gerardo Rosati; Sara Lonardi; Nicoletta Pella; Maria Banzi; Maria G. Zampino; Katia F. Dotti; Lorenza Rimassa; Paolo Marchetti; Evaristo Maiello; Fabrizio Artioli; Daris Ferrari; Roberto Labianca; Paolo Bidoli; Alberto Zaniboni; Alberto Sobrero; Vincenzo Iaffaioli; Sabino De Placido; Gian Luca Frassineti; Andrea Ciarlo; Angela Buonadonna; Nicola Silvestris; Elena Piazza; Lorenzo Pavesi; Mauro Moroni; Mario Clerico; Massimo Aglietta; Paolo Giordani; Francesca Galli; Fabio Galli; Fausto Petrelli

    Venous thromboembolic events (VTE), which comprise deep vein thrombosis and pulmonary embolism, are a frequent complication in patients with cancer, and are associated with increased morbidity and mortality.1 Among the VTE assessment models, the Khorana risk score, developed by Khorana, is the best-validated model with which to stratify VTE risk in ambulatory patients with cancer.2 The Khorana score (KS) predicts thrombosis risk based on a collection of simple variables, including type of cancer, body mass index (BMI), and complete blood count (platelet, leukocyte, hemoglobin). Cancer patients with a KS of 3 or greater are at high risk for developing blood clots. However, KS applies to ambulatory cancer patients with metastatic disease and was never validated in an adjuvant setting.

    更新日期:2020-01-22
  • TROP2 overexpression in colorectal liver oligometastases is associated with poor prognosis after liver resection
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-12-31
    Jianhong Peng; Qingjian Ou; Yuxiang Deng; Binyi Xiao; Lin Zhang; Jibin Li; Yin Li; Desen Wan; Zhenhai Lu; Yujing Fang

    Currently, colorectal cancer (CRC) is one of the most common human malignant diseases in China and worldwide.1,2 The development of distant metastasis is a leading cause of treatment failure and disease-related deaths. The liver is the most common site of metastasis in CRC patients, and approximately 50% of patients ultimately develop liver metastases during the course of disease progression.3,4 Liver curative resection offers a phase of no evidence of disease (NED) and a chance for long-term survival for 50% of patients.5,6 Unfortunately, more than 60% of patients develop recurrent disease during the subsequent follow-up after the initial liver resection.7,8

    更新日期:2019-12-31
  • Pemetrexed/carboplatin plus gefitinib as a first-line treatment for EGFR-mutant advanced nonsmall cell lung cancer: a Bayesian network meta-analysis
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-12-30
    Zhonghan Zhang; Kangmei Zeng; Shen Zhao; Yuanyuan Zhao; Xue Hou; Fan Luo; Feiteng Lu; Yaxiong Zhang; Ting Zhou; Yuxiang Ma; Yunpeng Yang; Wenfeng Fang; Yan Huang; Li Zhang; Hongyun Zhao

    Lung cancer remains the leading cause of cancer incidence and cancer-related mortality worldwide.1 The most prevalent type is nonsmall cell lung cancer (NSCLC), accounting for 85% of all lung cancers.2

    更新日期:2019-12-30
  • Eribulin mesylate use as third-line therapy in patients with metastatic breast cancer (VESPRY): a prospective, multicentre, observational study
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-12-19
    Vincenzo Adamo; Giuseppina Rosaria Rita Ricciardi; Dario Giuffrida; Giuseppa Scandurra; Antonio Russo; Livio Blasi; Pietro Spadaro; Carmelo Iacono; Hector J. Soto Parra; Antonino Savarino; Francesco Ferraú; Filippo Zerilli; Francesco Verderame; Alfredo Butera; Carlo Santangelo; Veronica Franchina; Michele Caruso

    Despite improvements in treatment, metastatic breast cancer (MBC) is still an incurable disease, with poor long-term survival and a 5-year survival rate lower than 25%.1 Patients with MBC are often resistant to anthracyclines and taxanes, usually used as first-line therapies, and even when these agents can be used, treatment failure occurs in most cases.2 However, cytotoxic chemotherapy remains the mainstay approach for MBC, especially for women with hormone-receptor positive breast cancer refractory to endocrine therapy and visceral crisis, and those with triple-negative BC. Treatments are aimed mainly at stabilizing or reducing the total disease burden, extending life expectancy and preserving quality of life.3 Among therapeutic options currently available to manage heavily pretreated patients with MBC, eribulin could be effective in patients with disease resistant to other tubulin-targeting agents. Unlike taxanes, eribulin inhibits only microtubule polymerization and blocks mitosis in G2-M phase, inducing apoptosis.4

    更新日期:2019-12-19
  • Regorafenib in glioblastoma recurrence: how to deal with conflicting ‘real-life’ experiences?
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-12-16
    Martin Glas; Sied Kebir

    To date, treatment options for glioblastoma recurrence are scarce. Based on efficacy data from randomized clinical trials, the nitrosourea compound CCNU (lomustine) is considered standard treatment after temozolomide failure. Treatment with lomustine in recurrent glioblastoma yields median overall survival (mOS) ranging from 8.6–9.8 months and median progression-free survival (mPFS) from 1.5–2.7 months.1–3 In a recently published open-label, randomized, phase II trial (REGOMA trial) of patients with first glioblastoma recurrence, regorafenib was found superior to lomustine with mOS of 7.4 months in regorafenib-treated patients as opposed to 5.6 months in lomustine treated patients.4 The radiographically assessed disease control rate (defined as complete/partial response or stable disease) was 44% in the regorafenib arm and 20% in the lomustine control arm. A yet unanswered question is whether regorafenib is going to replace lomustine as standard treatment should regorafenib superiority be confirmed in a planned randomized phase III trial.

    更新日期:2019-12-17
  • Hormonal treatment combined with targeted therapies in endocrine-responsive and HER2-positive metastatic breast cancer
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-12-16
    Emilia Montagna; Marco Colleoni

    The human epidermal growth factor receptor 2 (HER2) is a member of the membrane tyrosine kinase receptor family (i.e. HER1-4), amplified or overexpressed in 20–25% of breast cancers.1

    更新日期:2019-12-17
  • NF-κB activation triggers NK-cell stimulation by monocyte-derived dendritic cells
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-12-11
    Naomi C. Bosch; Reinhard E. Voll; Caroline J. Voskens; Stefanie Gross; Barbara Seliger; Gerold Schuler; Niels Schaft; Jan Dörrie

    Dendritic cells (DCs) play a vital role in the immune system. They build the bridge between the adaptive and innate immune system because they can activate both T cells via major histocompatibility complex (MHC) presentation of antigens in conjunction with co-stimulatory signals1 and the innate immune system such as NK cells.2 Therefore, DCs have been used for therapeutic tumor vaccination with the primary goal of activating cytotoxic T lymphocytes (CTLs) to enable elimination of tumor cells.3 Recently, evidence emerged that not only adaptive immune responses, but also the activation of the innate immune system is important to fight against the malignant tissue.4,5 NK cells activated by vaccine DCs can: (a) induce the maturation of further DCs,6,7 which in turn leads to additional activation of CTLs in a CD4+ T cell-independent manner,8 (b) directly activate additional naïve T cells through IFNγ secretion,9 and (c) attack and directly kill tumor cells,10 which can then lead to a T-cell cross-presentation of released tumor material by DCs.11

    更新日期:2019-12-13
  • A phase II study of the efficacy and safety of the MET inhibitor capmatinib (INC280) in patients with advanced hepatocellular carcinoma
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-12-11
    Shukui Qin; Stephen Lam Chan; Wattana Sukeepaisarnjaroen; Guohong Han; Su Pin Choo; Virote Sriuranpong; Hongming Pan; Thomas Yau; Yabing Guo; Minshan Chen; Zhenggang Ren; Jianming Xu; Chia-Jui Yen; Zhong-Zhe Lin; Luigi Manenti; Yi Gu; Yongjian Sun; Ralph Tiedt; Lu Hao; Wenjie Song; Tawesak Tanwandee

    According to the World Health Organization, hepatocellular carcinoma (HCC) is the fifth most common malignancy and the second major cause of tumor-related death in the world today.1 Although HCC is being diagnosed earlier, patients with advanced HCC have poor long-term survival, and the incidence and mortality rates are rising.2,3 Activation (overexpression, amplification, or both) of the MET signaling pathway [where the MET gene encodes MET/hepatocyte growth factor (HGF) receptor protein] has been observed in 20–48% of patients with HCC,4 which was determined using a variety of methods, including greater than median density by Western blotting, increased MET gene expression signature, MET copy number (CN) gain and mRNA expression, and positive (>20% of tumor section) immunohistochemistry (IHC) staining.4–9 In addition, overexpression by these criteria was shown to predict shorter survival in patients with HCC.4–7 The MET receptor tyrosine kinase binds its sole ligand HGF, which then activates the RAS mitogen-activated protein kinase (MAPK) pathway, phosphatidylinositol-3 kinase (PI3K)-protein kinase B (PKB or AKT) pathway, mammalian target of rapamycin pathway, signal transducer and activator of transcription (STAT) pathway, beta-catenin pathway, and Notch pathway. Activation of the MET signaling pathway, therefore, promotes cell proliferation, survival, and metastasis.10,11 Experimental evidence demonstrated that MET inhibition abrogates the growth of MET-activated HCC cells by blocking MET phosphorylation and the activation of the downstream PI3K and MAPK pathways.12 In addition, overexpression of HGF and MET amplification has been shown to predict the sensitivity of human HCC xenografts to MET inhibition.13

    更新日期:2019-12-11
  • An RB-1 loss of function gene signature as a tool to predict response to neoadjuvant chemotherapy plus anti-HER2 agents: a substudy of the NeoALTTO trial (BIG 1-06)
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-12-11
    Emanuela Risi; Chiara Biagioni; Matteo Benelli; Ilenia Migliaccio; Amelia McCartney; Martina Bonechi; Cristina Guarducci; Florentine Hilbers; Serena Di Cosimo; Jens Huober; Dario Romagnoli; Giulia Boccalini; Stefania Vitale; Christos Sotiriou; Laura Biganzoli; Angelo Di Leo; Luca Malorni

    Of all invasive breast cancers, approximately 20% present with, and are characterized by, human epidermal growth factor receptor 2 (HER2) over-expression and/or HER2 gene amplification.1 Anti-HER2 agents (H) given in combination with chemotherapy (CT) represent the current standard of care for patients with early HER2+ breast cancer.2 The phase III neoadjuvant NeoALTTO trial showed that pathological complete response (pCR) rates were significantly improved in patients who received paclitaxel plus dual HER2 blockade by way of the anti-HER2 monoclonal antibody, trastuzumab, plus the small molecule tyrosine kinase inhibitor, lapatinib, compared with paclitaxel plus either anti-HER2 agent alone.3,4 This outcome was observed across all subgroups; however, a meaningful difference in terms of response was observed between hormone receptor positive (HR+) and HR negative (HR–) tumours, in favour of the latter.3 Similar results have been reported by several other neoadjuvant trials, confirming that a substantial proportion of patients with HR+/HER2+ disease do not respond to H combined with CT.5–8 Preclinical data suggest that this difference in response between HR+ and HR– tumours could be partly attributed to bidirectional crosstalk between the ER and HER2 pathways and as such, targeting both pathways simultaneously may be a superior therapeutic strategy than therapy directed at a single pathway.9 Clinical trials have examined the addition of endocrine therapy (ET) to H in both early and advanced HR+/HER2+ breast cancer, consistently showing a significant benefit from the combination.10–17 However, whether the combination of ET and H would prove superior to the clinically established combination of H and CT remains an open question, as there have been no direct comparisons made between these two approaches. In addition to HR expression, different molecular features also contribute to the heterogeneous response to treatment observed in HER2+ tumours. Gene expression profiling by PAM50 can divide HER2+ breast cancers into five intrinsic molecular subtypes (luminal-A, luminal-B, HER2-enriched, basal-like and normal-like) with a different subtype distribution between HR+ and HR– tumours. Several neoadjuvant trials have shown HER2-enriched (HER2-e) disease is associated with the highest pCR rate after CT in combination with H, out of the four molecular subtypes.8,12,18

    更新日期:2019-12-11
  • Cytotoxic impact of a perillyl alcohol–temozolomide conjugate, NEO212, on cutaneous T-cell lymphoma in vitro
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-12-06
    Catalina Silva-Hirschberg; Hannah Hartman; Samantha Stack; Steve Swenson; Radu O. Minea; Michael A. Davitz; Thomas C. Chen; Axel H. Schönthal

    Primary cutaneous lymphomas are a heterogenous group of extranodal non-Hodgkin lymphomas. In contrast to nodal non-Hodgkin lymphomas, most of which are B-cell derived, approximately 75% of primary cutaneous lymphomas are T-cell derived.1 Cutaneous T-cell lymphomas (CTCLs) are rare and they are characterized by the presence of malignant T lymphocytes in the skin.2,3 They represent 3.9% of all non-Hodgkin lymphomas with an annual incidence of 6.4–9.6 cases per million people in the United States.4–6 Mycosis fungoides (MF) is the most common CTCL, whereas Sézary syndrome (SS) is much rarer. They account for 2–3% of all lymphomas7 and comprise approximately 53% of all cutaneous lymphomas.4 MF has an annual incidence of 5.6 per million persons3 representing 50% of all CTCLs,8 whereas SS has an annual incidence of 0.1–0.3 per million persons and represents 2.5% of all CTCLs.9

    更新日期:2019-12-06
  • Effectiveness of stereotactic ablative radiotherapy in patients with advanced hepatocellular carcinoma unsuitable for transarterial chemoembolization
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-12-04
    Hsin-Lun Lee; Jo-Ting Tsai; Chun-You Chen; Ying-Chun Lin; Chin-Beng Ho; Lai-Lei Ting; Chia-Chun Kuo; I-Chun Lai; Chun-Yu Lin; Jui-Hsiang Tang; Yu-Min Huang; Wei-Yu Kao; Sheng-Wei Cheng; Chia-Ning Shen; Shang-Wen Chen; Jeng-Fong Chiou

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. HCC is more common in the Asia-Pacific region than in other regions due to the higher prevalence of chronic hepatitis B virus infection in this region.1,2 Although surgical intervention and liver-directed nonsurgical therapies remain the mainstay of treatment for early-to-intermediate stage HCC, patients with HCC are typically diagnosed in the advanced stages of the disease, which are characterized by the presence of symptoms, portal vein thrombosis (PVT), or extrahepatic spread, for which radical treatments are often unfeasible and systemic therapy is the major treatment.1,3–6 Traditionally, since 2008, the tyrosine kinase inhibitor sorafenib has been the only standard treatment indicated for patients with HCC with Barcelona Clinic Liver Cancer (BCLC) stage C.7,8 Recently, systemic therapies, including multikinase and immune checkpoint inhibitors, have rapidly evolved and are now capable of prolonging the survival of patients with advanced HCC.1 However, intrahepatic tumor progression with consequent liver failure is the major cause of treatment failure.9,10

    更新日期:2019-12-04
  • The emerging role of CDK4/6i in HER2-positive breast cancer
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-11-27
    Ciara C. O’Sullivan; Vera J. Suman; Matthew P. Goetz

    Breast cancer (BC) is the most frequently diagnosed malignancy in women, accounting for approximately 25% of cancer diagnoses and 15% of cancer-related deaths in women, globally.1 Approximately 15–20 % of BCs are classified as human epidermal growth-factor receptor 2 (HER2) positive (HER2+).2 Prior to the development of HER2-directed therapies, a diagnosis of HER2+ BC was associated with a poor prognosis. In the late 1990s, the addition of trastuzumab, a monoclonal antibody targeting HER2, to standard chemotherapy regimens resulted in marked improvements in disease-free survival (DFS) and overall survival (OS) in both the adjuvant and metastatic settings.3 This has led to the development of other effective HER2-directed therapies, including lapatinib (a dual tyrosine-kinase inhibitor) pertuzumab (an HER2/HER3-dimerization inhibitor), ado-trastuzumab emtansine (T-DM1, an antibody–drug conjugate) and neratinib (an irreversible pan-HER inhibitor).4,5

    更新日期:2019-11-28
  • Targeted therapies for advanced bladder cancer: new strategies with FGFR inhibitors
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-11-25
    Chiara Casadei; Nazli Dizman; Giuseppe Schepisi; Maria Concetta Cursano; Umberto Basso; Daniele Santini; Sumanta K. Pal; Ugo De Giorgi

    Bladder cancer (BC) is a common cancer worldwide whose incidence has increased in recent years. In Europe, the age-standardized incidence rate of BC is 9.0 for men and 2.2 for women.1 BC can be divided into non-muscle-invasive (NMIBC) and muscle-invasive tumors (MIBC). Approximately 90% of all MIBC are urothelial carcinomas (UC). At diagnosis, 75% of UC are NMIBC, while 25% of cases are MIBC or metastatic disease.2 In an estimated 5–8% of cases, UC originates in the renal pelvis or ureter (upper tract urothelial carcinoma, UTUC).3 Patients with advanced UC are not treatable with curative intent. The first-line standard of care is cisplatin-containing chemotherapy such as gemcitabine-cisplatin or M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin), both of which are characterized by similar efficacy but with a better safety profile for the former.4,5 However, about 30% of patients are not candidates for cisplatin due to renal dysfunction, poor performance status (PS), or other comorbidities.6 Alternative chemotherapeutic regimens, such as carboplatin-based therapies, correlate with inferior outcomes.7,8 Traditionally, the median overall survival (OS) ranged between 14 and 16 months in patients with advanced UC treated with platinum-based regimens, and long-term survival was rare.2,4

    更新日期:2019-11-26
  • Second-line treatment of EGFR T790M-negative non-small cell lung cancer patients
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-11-25
    Bin-Chi Liao; Sebastian Griesing; James Chih-Hsin Yang

    First- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), including gefitinib, erlotinib, afatinib, and dacomitinib, are effective as first-line treatment for advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutations (e.g. deletions in exon 19 and the exon 21 L858R mutation).1–7 EGFR T790M mutation emerges following EGFR-TKI therapy, and accounts for 55% of mechanisms of acquired resistance to first- and second-generation EGFR-TKIs.8–11 Osimertinib monotherapy is the currently recommended second-line treatment for EGFR T790M mutation-positive (T790M-pos) NSCLC.12–14 Other secondary resistance mutations in EGFR, such as D761Y, T854A, and L747S, are rare, and the irreversible EGFR-TKIs, afatinib and osimertinib, have been shown to inhibit EGFR phosphorylation in cells harboring these secondary mutations.15–18 For patients with EGFR T790M mutation-negative (T790M-neg) NSCLC, platinum-based chemotherapy is the currently recommended second-line treatment.19–21 In addition to the T790M resistance mutation, the molecular alternations identified as resistance mechanisms include bypass pathway activation [e.g. MET amplification [MET-amp] and HER2 amplification (HER2-amp)] and downstream signaling pathways (e.g. PI3K and BRAF mutations). Histological transformations [e.g. small cell and epithelial–mesenchymal transition (EMT)] are also mechanisms of resistance. T790M-neg NSCLC comprises these mechanisms plus other unknown mechanisms and is seen in a heterogeneous group of patients. In the era of molecular targeted therapy, immunotherapy, next-generation sequencing (NGS), and liquid biopsy, exploratory strategies are under development to identify patients suitable for molecular targeted therapy to overcome resistance mechanisms.

    更新日期:2019-11-26
  • Neoadjuvant therapy of locally/regionally advanced melanoma
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-07-31
    Arjun Khunger; Zachary S. Buchwald; Michael Lowe; Mohammad K. Khan; Keith A. Delman; Ahmad A. Tarhini

    Melanoma is increasing in incidence at a rate that exceeds that of all other malignancies.1 In 2019, in the United States, it is estimated that 96,480 new cases of melanoma will be diagnosed and 7230 will die as a result of this disease.1 The American Joint Committee on Cancer (AJCC) divides cutaneous melanoma into four stages.2 Stage I melanoma has the best prognosis with surgical treatment alone and a 10-year survival rate of about 94–98%.2 The 5-year post-surgical relapse rate in patients with stages IIA, IIB, and IIC ranges from over 20% to over 50%, whereas for patients with stage III melanoma and clinically detectable regional lymph nodes with or without in-transit metastases, the reported 5-year relapse rate is 68–89%.3–5

    更新日期:2019-11-18
  • Targeting CDK9 and MCL-1 by a new CDK9/p-TEFb inhibitor with and without 5-fluorouracil in esophageal adenocarcinoma
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-07-25
    Zhimin Tong; Alicia Mejia; Omkara Veeranki; Anuj Verma; Arlene M. Correa; Rashmi Dokey; Viren Patel; Luisa Maren Solis; Barbara Mino; Riham Kathkuda; Jaime Rodriguez-Canales; Steven H. Lin; Sunil Krishnan; Scott Kopetz; Mariela Blum; Jaffer A. Ajani; Wayne L. Hofstetter; Dipen M. Maru

    Preoperative chemotherapy or chemoradiation followed by surgery have improved survival outcomes and the likelihood of margin-negative esophagogastrectomy in patients with locoregional esophageal adenocarcinoma (EAC).1 However, these patients’ 5-year survival rates remain low.2,3 Biomarker-driven targeted therapies have had limited success in EAC patients, primarily in less than 20% of those with stage IV human epidermal growth factor receptor 2 (Her2-neu)-overexpressing disease who receive trastuzumab.4–6 To date, no targeted agent has demonstrated benefit as an adjunct to 5-fluorouracil-based chemotherapy or chemoradiation in patients with locally advanced EAC.

    更新日期:2019-11-18
  • Pilot study of bevacizumab in combination with docetaxel and cyclophosphamide as adjuvant treatment for patients with early stage HER-2 negative breast cancer, including analysis of candidate circulating markers of cardiac toxicity: ICORG 08–10 trial
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-07-24
    Giuseppe Gullo; Alex J. Eustace; Alexandra Canonici; Denis M. Collins; Michael J. Kennedy; Liam Grogan; Oscar Breathhnach; John McCaffrey; Maccon Keane; Michael J. Martin; Rajnish Gupta; Gregory Leonard; Miriam O’Connor; Paula M. Calvert; Paul Donnellan; Janice Walshe; Enda McDermott; Kathleen Scott; Andres Hernando; Imelda Parker; David W. Murray; Alice C. O’Farrell; Ashwini Maratha; Patrick Dicker; Mairin Rafferty; Verena Murphy; Norma O’Donovan; William M. Gallagher; Bonnie Ky; Dimitrios Tryfonopoulos; Brian Moulton; Annette T. Byrne; John Crown

    Angiogenesis is one of the hallmarks of cancer, and anti-angiogenic drugs have been the focus of intense study in clinical trials. Vascular endothelial growth factor (VEGF) occupies a central regulatory role in the process of angiogenesis. High levels of circulating VEGF predict a poor prognosis in cancer patients.1 The VEGF family consists of several signal protein variants and their receptors. Among them, the interaction between VEGF-A and VEGF receptor (VEGFR) subtype 2 is predominant in the formation of new blood vessels. Several studies have found a significant correlation between VEGF expression and clinical outcome in breast cancer (BC), with disease-free survival (DFS) and overall survival (OS) being significantly worse among those patients who have cancers overexpressing VEGF.2 Micro-metastases seem to depend on angiogenesis,3 therefore, targeting the anti-angiogenic switch before tumour vascularization, in the adjuvant setting when few pro-angiogenic factors are involved, has been hypothesized as an appropriate setting for anti-angiogenic therapy.

    更新日期:2019-11-18
  • Immunotherapy for hepatocellular carcinoma: recent advances and future perspectives
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-07-23
    Weiqi Xu; Ken Liu; Minjiang Chen; Jin-Yu Sun; Geoffrey W McCaughan; Xiao-Jie Lu; Jiansong Ji

    Hepatocellular carcinoma (HCC) notoriously has a poor prognosis. It is currently the fifth most common malignancy and the second leading cause of cancer-related death worldwide.1,2 Current first-line systemic therapy, such as sorafenib, can only extend the overall survival of patients with advanced HCC by 3 months and is associated with significant adverse effects.3 Although HCC is an immunogenic cancer that expresses various tumor associated antigens (TAAs), immune therapies have not demonstrated meaningful efficacy against HCC for decades.4 Interest in immune therapies was recently reinvigorated by the success of a programmed cell death protein 1 (PD-1) blockade observed in the treatment of advanced melanoma first reported in 2010.5 Since then, several monoclonal antibodies directed against the immune inhibitory molecules PD-1, programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), have been trialed, with promising antitumor immune responses seen against many solid tumors from bench to bedside.

    更新日期:2019-11-18
  • A real-world analysis of second-line treatment options in pancreatic cancer: liposomal-irinotecan plus 5-fluorouracil and folinic acid
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-07-17
    Markus Kieler; Matthias Unseld; Daniela Bianconi; Werner Scheithauer; Gerald W. Prager

    Pancreatic ductal adenocarcinoma (PAC) is a lethal disease with a devastating 5-year overall survival (OS) of approximately 7%. Although, just 4% of all malignant diseases are attributed to PAC, it is projected to become the second leading cause of cancer-related deaths in the United States before 2030.1 Since the introduction of the new chemotherapy regimens including albumin-bound paclitaxel (nab-paclitaxel) plus gemcitabine and FOLFIRINOX, after the gemcitabine monotherapy era, survival of patients with PAC has improved.2,3 This led to a change in the before rather theoretical debate about second-line treatment in the management of PAC and opened the clinical field for the exploration of continuum of care strategies. In 2015, there was the first approval of a second-line treatment option for patients with advanced PAC who have been previously treated with gemcitabine-based chemotherapy based upon the results of the phase III NAPOLI-1 trial.4 In this trial, 417 patients with metastatic PAC were randomized to three treatment arms and the combination treatment with nanoliposomal irinotecan (nal-IRI) and 5-fluorouracil/leucovorin (5-FU/LV) demonstrated superior survival compared with 5-FU/LV monotherapy (median OS of 6.1 versus 4.2 months; p = 0.012).

    更新日期:2019-11-18
  • TIMP-3 as a therapeutic target for cancer
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-07-16
    Chun-Wen Su; Chiao-Wen Lin; Wei-En Yang; Shun-Fa Yang

    Despite recent improvements, cancer treatment remains associated with several challenges. Cancer development is a multifactorial and multistep process and involves several genetic and epigenetic regulations. In addition, cancer cells possess several unique characteristics, also known as the cancer hallmark, that confer the cells with resistance against the human immune system and cancer treatment. The cancer hallmark includes tumor-promoting inflammation, enabling replicative immortality, avoiding immune destruction, evading growth suppressors, sustaining proliferative signaling, deregulating cellular energetics, resisting cell death, genome instability and mutation, inducing angiogenesis, and activating invasion and metastasis.1,2 Metastasis, which is the major cause of death among cancer patients, involves multiple processes including extracellular matrix (ECM) remodeling and degradation. Degradation of the ECM is required for tumor cell metastasis; this is achieved by several proteinases such as the plasmin system and particularly, the matrix metalloproteinases (MMPs).3–6 MMPs are known to play an important role in the tissue invasion and metastasis of cancer cells. The tissue inhibitors of MMPs (TIMPs) are endogenous inhibitors of MMPs, and regulation of MMPs by TIMPs is particularly important for the maintenance of the ECM. Disruption of the balance between the activities of MMPs and TIMPs during carcinogenesis may affect invasion and metastasis7–9 and may worsen patient outcomes.10 TIMP-3, a member of the TIMP family, is a 24-kDa secreted glycoprotein, and its gene is located on chromosome 22q12.1–q13.2. Knockout of the TIMP-3 gene in mice resulted in increased MMP, a disintegrin and MMPs with thrombospondin motifs (ADAMTS) activity, and cartilage degradation, suggesting that reduced TIMP-3 levels may cause osteoarthritis.11 In addition, the absence of TIMP-3 leads to poor cardiac remodeling and has been associated with myocardial infarction or hypertension.12,13 In cancer studies, TIMP-3 plays an important role in the cancer hallmark by controlling cell death, angiogenesis, tumor inflammation, and tumor cell invasion and dissemination.14 For instance, TIMP-3 restoration in cancer cells inhibits cell growth and promotes cell apoptosis.15,16 In addition, TIMP-3 overexpression improves the sensitivity of osteosarcoma to clinical drug treatment through interleukin (IL)-6 inhibition.17 TIMP-3 also acts as a potential antiangiogenesis agent by inhibiting endothelial cell tube formation.18 Moreover, TIMP-3 can inhibit cancer cell migration, invasion, and metastasis in vitro and in vivo.19,20 Clinical studies have reported reduced TIMP-3 expression in cases of several cancer types compared with normal controls;19–22 the loss of TIMP-3 may lead to poor outcomes, including large tumor size, high tumor stage, and metastasis.23–25 Herein, we review the structure and function of TIMP-3 and discuss its contribution to carcinogenesis and its potential in cancer therapy.

    更新日期:2019-11-18
  • The risk of liver cancer in autoimmune liver diseases
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-07-12
    Ana Lleo; Ynto S. de Boer; Rodrigo Liberal; Massimo Colombo

    According to Global Disease Burden, in 2015 there were 854,000 incident cases of liver cancer and 810,000 deaths globally, contributing to 20,578,000 disability-adjusted life-years (DALYs).1 Liver cancer stands as the fourth leading cause of cancer death after lung, colorectal, and stomach cancer and, in the last three decades, its incidence has increased by 75%. Interestingly, half of cases can be explained by changing population age structures, one-third by population growth, and less than 10% by changing age-specific incidence rates. While chronic infection with hepatitis B virus accounted for one-third of liver cancer deaths, alcohol was implicated in another 30%, hepatitis C in 21%, and other causes in 16%.

    更新日期:2019-11-18
  • The endonuclease APE1 processes miR-92b formation, thereby regulating expression of the tumor suppressor LDLR in cervical cancer cells
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-07-10
    Yi Sun; Yun Feng; Guiqian Zhang; Ya Xu

    RNA damage induced by missing bases [e.g. by generation of apurinic/apyrimidinic (AP) sites], or by modification of bases (e.g. by oxidative damage), can alter RNA function and is increasingly found to participate in carcinogenesis.1 For instance, mRNA damaged by oxidation or AP-site formation can interfere with translational accuracy.1 In the case of microRNAs (miRNAs), oxidation can alter their regulatory activity, thus modifying expression of target genes.2 Consequently, degradation of damaged miRNAs in genotoxic environments can have significant repercussions in oncogenesis and for the development of chemoresistance in existing tumors.

    更新日期:2019-11-18
  • Third-line systemic treatment in advanced/metastatic gastric cancer: a comprehensive review
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-06-29
    Wing-lok Chan; Ka-on Lam; Tsz-him So; Victor Ho-fun Lee; Lai-wan Dora Kwong

    Gastric cancer is the fifth commonest cancer and remains the world’s third leading cause of cancer mortality.1 Surgery is the mainstay of curative treatment in stage I to III gastric cancers. However, more than half of the patients at diagnosis are already too advanced for curative resection. Even for those who are resectable upfront, the recurrence rate is still high at around 40–80%.2,3

    更新日期:2019-11-18
  • Overcoming platinum-acquired resistance in ovarian cancer patient-derived xenografts
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-06-24
    Francesca Ricci; Laura Brunelli; Roberta Affatato; Rosaria Chilà; Martina Verza; Stefano Indraccolo; Francesca Falcetta; Maddalena Fratelli; Robert Fruscio; Roberta Pastorelli; Giovanna Damia

    Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer with more than 14,000 deaths/year in western countries.1 The high mortality is mostly due to the frequent presentation at advanced stage, and to primary or acquired resistance to platinum-based therapy. Different studies based on whole-genome, proteomic or transcriptomic profiling studies have defined some of the mechanisms involved in the development of platinum resistance in ovarian cancer.2–4 However, these results have not yet been translated into effective therapeutic strategies to prevent or overcome platinum resistance.

    更新日期:2019-11-18
  • Next-generation sequencing and biomarkers for gastric cancer: what is the future?
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-06-21
    Akihito Kawazoe; Kohei Shitara

    Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related mortality worldwide.1 Although some chemotherapy (CTx) regimens, including a platinum + fluoropyrimidine combination, trastuzumab [for human epidermal growth factor receptor 2 (HER2)-positive cases], taxanes, irinotecan and ramucirumab, reportedly enhance the survival outcomes of patients with advanced GC (AGC),2–6 the prognosis remains poor (median survival ~1 year). Although the phase III ATTRACTION-2 trial of anti-programmed death 1 (anti-PD-1) antibody, nivolumab, reported a survival benefit in AGC,7 the overall response rate (ORR) was approximately 10% and half of the patients exhibited early disease progression. Thus, the establishment of a better selection of patients who might derive greater benefit from PD-1 blockade is warranted. In addition, trifluridine/tipiracil (TAS-102) demonstrated a survival benefit compared with placebo in heavily pretreated patients with AGC.8 However, until recently, several phase III trials of targeting agents for AGC failed to demonstrate a survival benefit (Table 1). Notably, single-agent activity for AGC is minimal, and a few trials have attempted to identify possible biomarkers before phase III trials; thus, better patient stratification based on molecular profiles is crucial.

    更新日期:2019-11-18
  • Ketogenic diet treatment as adjuvant to standard treatment of glioblastoma multiforme: a feasibility and safety study
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-06-21
    Elles J. T. M. van der Louw; Joanne F. Olieman; Patricia M. L. A. van den Bemt; Jacoline E. C. Bromberg; Esther Oomen-de Hoop; Rinze F. Neuteboom; Coriene E. Catsman-Berrevoets; Arnaud J. P. E. Vincent

    The median survival duration of patients with glioblastoma multiforme (GBM) is 15 months after multimodal therapy combining surgery, radiotherapy (RT) and chemotherapy (CT).1 As high-grade glioma cells consume mainly glucose,2 dietary carbohydrate restriction has been suggested as a possible therapeutic strategy to improve the survival duration.3,4 In recent in vitro and in vivo studies, cancer growth was inhibited by the ketosis and increased lipolysis induced by low-carbohydrate diets.5–7 It seems, therefore, that GBM cells do not compensate for glucose restriction, whereas normal brain cells do so by metabolizing ketone bodies. Apoptosis may potentially occur under carbohydrate restriction.8,9 An extremely carbohydrate-restricted diet, the ketogenic diet (KD; high-fat, low-carbohydrate diet), could be of interest because it mimics the metabolic response to starvation when ketones become the main fuel for the brain. Although low-carbohydrate intake alone has been found effective on survival in the treatment of GBM in several animal models and in vitro studies, combining current therapies with KD was even more effective.10 For example, the KD as adjuvant to radiation therapy in mice with GBM showed an impressive synergistic effect as compared with RT alone. The underlying mechanism is not yet clarified but this effect is presumed to be higher due to radiation cytotoxicity as a result of sensitization of the tumor cells by KD.10

    更新日期:2019-11-18
  • Phase Ib study of the combination of pexidartinib (PLX3397), a CSF-1R inhibitor, and paclitaxel in patients with advanced solid tumors
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-06-21
    Robert Wesolowski; Neelesh Sharma; Laura Reebel; Mary Beth Rodal; Alexandra Peck; Brian L. West; Adhirai Marimuthu; Paul Severson; David A. Karlin; Afshin Dowlati; Mai H. Le; Lisa M. Coussens; Hope S. Rugo

    Colony stimulating factor 1 receptor (CSF-1R) signaling has been implicated in homing of monocytes to the tumor microenvironment and their differentiation to tumor associated macrophages (TAMs). TAMs induce immune suppression and neo-angiogenesis, facilitating tumor growth and metastases. Work in a mouse model of mammary carcinoma revealed that following exposure to chemotherapy, malignant cells increase expression of colony stimulating factor (ligand of CSF-1R) leading to recruitment of TAMs and chemotherapy resistance. Pexidartinib, a small molecule inhibitor of CSF-1R (IC50 17 nM), was shown to abrogate TAM recruitment following chemotherapy, and this was associated with a less suppressed immune tumor microenvironment, slower tumor growth, and improved survival of study animals. Here, we present the results of the first-in-human phase Ib study, which established recommended phase II dose of pexidartinib in combination with paclitaxel in patients with advanced, treatment refractory solid tumors.

    更新日期:2019-11-18
  • Molecular targeted therapy of BRAF-mutant colorectal cancer
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-06-18
    Michel Ducreux; Ali Chamseddine; Pierre Laurent-Puig; Cristina Smolenschi; Antoine Hollebecque; Peggy Dartigues; Emmanuelle Samallin; Valérie Boige; David Malka; Maximiliano Gelli

    Colorectal cancer (CRC) remains one of the main causes of cancer mortality around the world. Although global mortality is decreasing, an increased mortality in young adults (<50 years old) has been reported.1 Virus-induced rapidly accelerated fibrosarcoma (v-RAF) was first identified as an oncogene through the cloning of a viral mouse gene that had the ability to transform NIH3T3 cells. Its human ortholog CRAF (RAF-1) and subsequently the related kinase genes ARAF and BRAF were later found to be commonly mutated in cancer. This RAF kinase family consists of key components of the RAS–RAF–MEK–ERK signaling cascade (MAPK pathway; Figures 1 and 2). The BRAF (v-RAF murine sarcoma viral oncogene homolog B; B-type raf kinase) gene is located on chromosome 7. Like RAS, the serine/threonine-protein kinase BRAF is a downstream signaling protein in the epidermal growth factor receptor (EGFR)-mediated pathway; in vitro experiences have highlighted that some genes are differently expressed in BRAF-mutant and wild-type CRC cell lines.2,3 A characteristic gene expression signature associated with BRAF mutation has been identified.4 However, attempts to directly inhibit the active BRAF protein failed in metastatic CRC (mCRC),5 suggesting a more complex (or at least different) carcinogenic process in this disease. Nevertheless, BRAF mutation testing is now recommended for mCRC in the latest National Comprehensive Cancer Network guidelines.6 We will discuss and review here the more recent literature that specifically concerns BRAF-mutant CRC.

    更新日期:2019-11-18
  • EGFR-AS1/HIF2A regulates the expression of FOXP3 to impact the cancer stemness of smoking-related non-small cell lung cancer
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-06-13
    Haolong Qi; Shanshan Wang; Juekun Wu; Shucai Yang; Steven Gray; Calvin S.H. Ng; Jing Du; Malcolm J. Underwood; Ming-Yue Li; George G Chen

    Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung malignances and median survival is only 6–12 months.1 It is well accepted that the development of all malignancies including metastasis and their low sensitivity to antitumor treatments could be attributed to the cancer stem cells (CSCs), which have the ability to initiate and colonize at distant secondary tissue sites.2–7 Among the various molecular signaling pathways in cells, Notch, WNT, and hedgehog are the three main pathways that are believed to be related to cancer stemness.2,4–7 Understanding the key signaling pathways of lung CSCs is of pivotal and clinical importance for new drug discovery and development.2

    更新日期:2019-11-18
  • CD8+ PD-1+ T-cells and PD-L1+ circulating tumor cells in chemotherapy-naïve non-small cell lung cancer: towards their clinical relevance?
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-06-12
    Athanasios Kotsakis; Galatea Kallergi; Despoina Aggouraki; Zaharoula Lyristi; Filippos Koinis; Eleni Lagoudaki; Anastasios Koutsopoulos; Vassilis Georgoulias; Eleni-Kyriaki Vetsika

    The immune system exerts a protective role against cancer, mainly via the capacity of the CD8+ cytotoxic T lymphocytes to recognize and kill cancer cells.1 However, cancer cells often develop mechanisms to escape the immune surveillance leading, thus, to the development of metastases.2 One of the escape mechanisms is the activation of the programmed cell death-1 (PD-1) receptor, an inhibitory immune checkpoint, mostly expressed on the surface of T-cells. The engagement between the PD-1 receptor and its ligands, PD-L1 or PD-L2,3 results in the suppression of effector cell function via the induction of anergy, apoptosis, inhibition of their proliferation and secretion of inflammatory cytokines such as interferon gamma (IFN-γ), interleukin (IL)-4 and IL-2.4 PD-1 and PD-L1 are typically expressed on both activated and exhausted immune cells (ICs) and are upregulated under the influence of IFN-γ.5

    更新日期:2019-11-18
  • The incidence and relative risk of adverse events in patients treated with bisphosphonate therapy for breast cancer: a systematic review and meta-analysis
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-06-09
    Yan-Li Yang; Zi-Jian Xiang; Jing-Hua Yang; Wen-Jie Wang; Ruo-Lan Xiang

    Breast cancer is the most common malignant cancer among women worldwide, in both developing and developed countries. The survival rate of breast cancer is highly correlated with the degree of disease at the time of diagnosis, with early stage disease conferring superior survival rates. However, the majority of patients with advanced breast cancer develop bone metastases.1 Some studies have reported that increased osteoclast activity in patients with breast cancer and breast cancer bone metastases leads to skeletal-related events (SREs), which include bone fractures, hypercalcemia, nerve compression, and severe pain.2 These skeletal complications, in turn, increase the need for palliative radiation or surgery to bone, limit functional independence, adversely affect quality of life, and continue to cause morbidity of the affected patients.3,4

    更新日期:2019-11-18
  • Targeting the SLIT/ROBO pathway in tumor progression: molecular mechanisms and therapeutic perspectives
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-06-06
    Zhengdong Jiang; Gang Liang; Ying Xiao; Tao Qin; Xin Chen; Erxi Wu; Qingyong Ma; Zheng Wang

    The formation of tumors is modulated by multiple soluble and immobilized molecular factors including proteases, growth factors, extracellular matrix components, etc. Increasing evidence has shown that tumors can mimic embryonic development. Therefore, multiple molecular cytokines that affect embryonic development have been investigated in cancer progression. The SLIT/ROBO pathway is particularly involved in embryonic development.1 Gara et al.2 reviewed the roles of the SLIT/ROBO pathway in different types of cancer, molecular crosstalk, and the modulation of oncogenic signaling pathways. Huang et al.3 summarized the SLIT/ROBO pathway and its biological significance in gastrointestinal cancers. Recent studies showed that the SLIT/ROBO pathway can produce both beneficial and detrimental effects in the growth of malignant cells. It seems that SLIT/ROBO play contradictory roles in tumorigenesis. Therefore, in this brief review, the tumor promotion and tumor suppression roles of the SLIT/ROBO pathway and its biological significance in cancer will be summarized.

    更新日期:2019-11-18
  • Identification of CSPG4 as a promising target for translational combinatorial approaches in osteosarcoma
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-06-06
    Federica Riccardo; Lidia Tarone; Selina Iussich; Davide Giacobino; Maddalena Arigoni; Federica Sammartano; Emanuela Morello; Marina Martano; Francesca Gattino; Raffaella De Maria; Soldano Ferrone; Paolo Buracco; Federica Cavallo

    Osteosarcoma (OSA) is the most common primary malignant tumor of the bones. Of note, OSA is the sixth most-frequent pediatric cancer and represents the second most common cause of cancer-related death in this age group; a second peak is observed in adults after the sixth decade of life.1,2 Currently, primary OSA is classified into low- (Grade I) and high-grade subtypes (Grade II and III in the presence of metastasis), high-grade OSA being the most prevalent and aggressive variant.3

    更新日期:2019-11-18
  • Patterns of treatment and outcome with 500-mg fulvestrant in postmenopausal women with hormone receptor-positive/HER2-negative metastatic breast cancer: a real-life multicenter Italian experience
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-06-04
    Raffaella Palumbo; Federico Sottotetti; Erica Quaquarini; Anna Gambaro; Antonella Ferzi; Barbara Tagliaferri; Cristina Teragni; Luca Licata; Francesco Serra; Pietro Lapidari; Antonio Bernardo

    Breast cancer, one of the three most common malignancies worldwide, is a disease strongly related with age, with the highest incidence among elderly, postmenopausal women.1 Approximately 70–80% of breast cancers are estrogen receptor (ER) or progesterone receptor (PgR)-positive and thus potentially sensitive to endocrine therapy (ET). The main international guidelines endorse ET as the preferred first-line option for hormone receptor-positive (HR+) disease in postmenopausal women, even in the presence of visceral disease (but not in cases of visceral crisis or concern/proof of endocrine resistance). At some point of her clinical history, every woman with HR+/HER2 metastatic breast cancer (MBC) will receive one or more ET lines in the context of a sequential strategy.2 The choice of the upfront and subsequent agents mainly depends on the type of adjuvant ET as well as the disease-free interval from its completion; these can be aromatase inhibitors (AIs), tamoxifen, or fulvestrant.3 However, almost all women with initially endocrine-sensitive disease will develop a resistance to ET, either as an early failure (de novo resistance), or as a progression after an initial response (acquired resistance).4 The optimal sequence of single endocrine agents and combinations with targeted agents is yet to be defined and is a research priority.

    更新日期:2019-11-18
  • Major innovations and clinical applications of disodium-levofolinate: a review of available preclinical and clinical data
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-06-04
    Margherita Ratti; Jens Claus Hahne; Laura Toppo; Emanuela Castelli; Fausto Petrelli; Rodolfo Passalacqua; Sandro Barni; Gianluca Tomasello; Michele Ghidini

    Since the beginning of its development, 5-fluorouracil (5-FU) has played a central role in the therapy of many solid cancers and is still a common therapeutic option especially in metastatic and adjuvant setting of colorectal and gastric tumours.1,2

    更新日期:2019-11-18
  • SOX11: friend or foe in tumor prevention and carcinogenesis?
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-06-03
    Zhi Yang; Shuai Jiang; Chenxi Lu; Ting Ji; Wenwen Yang; Tian Li; Jianjun Lv; Wei Hu; Yang Yang; Zhenxiao Jin

    Since its first description in 1990, the family of sex-determining region Y (SRY)-related high-mobility-group (HMG) box (SOX) transcription factors have gained attention for their potential physiological and pathological role in cell biology. The SOX family are characterized by their high degree of sequence homology with the SRY HMG DNA-binding domain.1,2 To date, approximately 20 SOX genes have been identified in both vertebrates and invertebrates, which can be further categorized into eight subgroups (SOXA to SOXH) based on sequence homology inside and outside the HMG domain.3 SOX transcription factors are essential in regulating stem cell maintenance and terminal differentiation of different cell types.4 Given that SOX proteins control multiple essential developmental and homeostatic processes, it is not surprising that dysfunction and mutation of SOX genes can lead to a variety of hereditary human diseases. Growing evidence has shown that several SOX members are involved in different types of cancer, such as SOX2 in prostate cancer (PCa),5 SOX4 in leukemia,6 and SOX9 in breast cancer.7

    更新日期:2019-11-18
  • Neoadjuvant zoledronic acid for HER2-positive breast cancer: the Zo-NAnTax trial
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-31
    Susanne Crocamo; Renata Binato; Bruno de Paula; Giselle Vignal; Lídia Magalhães; Roberta Sarmento; Maria Theresa Accioly; Isabele Small; Sandra Gioia; Pedro Maroun; Pamela Moutinho; Vivianne Freitas; Karuline Catein; Eliana Abdelhay

    Neoadjuvant therapy is indicated for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and is an option even for early tumors. Trastuzumab plus neoadjuvant chemotherapy increases the pathologic complete response (pCR) rate compared with chemotherapy alone in women with HER2-positive BC1 and is correlated with longer survival.2

    更新日期:2019-11-18
  • Treatments for patients with advanced neuroendocrine tumors: a network meta-analysis
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-29
    Tingting Liu; Jiehao Liao; Jun Dang; Guang Li

    Neuroendocrine tumors (NETs) are a heterogeneous class of neoplasms arising from neuroendocrine cells that are scattered throughout the body.1 Data from population-based registries indicate that the majority of NETs arise from the gastrointestinal tract, followed by lung and pancreas.1 Although the incidence of these tumors is increasing, NETs have usually been considered a rare entity. The World Health Organization (WHO) 2010 classification systems for the gastroenteropancreatic NETs categorize tumors as well-differentiated NETs that can be divided into grade 1 (Ki67 < 3%) and grade 2 (Ki67 3–20%), and poorly differentiated neuroendocrine carcinomas (Ki-67 > 20%).2 Radical surgery is the only curative treatment for NETs; however, only a low percentage of patients are suitable for surgery as more than 50% of patients have advanced disease at diagnosis.3

    更新日期:2019-11-18
  • The p53/miR-193a/EGFR feedback loop function as a driving force for non-small cell lung carcinoma tumorigenesis
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-23
    Wei Wang; Xia-Bo Shen; Wei Jia; Da-Bing Huang; Yong Wang; Yue-Yin Pan

    Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein that possesses intrinsic tyrosine kinase activity. EGFR signaling dysregulation is vital to tumor progression.1 EGFR is considered a cancer-driving gene that affects numerous systems involved in oncogenesis, including cell proliferation, DNA synthesis, cell cycle progression, invasion, and metastasis.2 Hyperactivation of the EGFR pathway in NSCLC has been shown to result in the development of many cancer characteristics, such as increased cell proliferation, migration, angiogenesis, metastasis, and increased cell survival by blocking apoptosis.3–5 Many chemical inhibitors of EGFR and EGFR-neutralizing antibodies have been developed for cancer therapy.6,7 However, their effects in the treatment of NSCLC are not very satisfactory likely because the mechanisms driving NSCLC progression are not fully understood.8 Thus, the detailed molecular mechanisms of the role of EGFR-related pathways in NSCLC progression remain to be elucidated.

    更新日期:2019-11-18
  • Olaparib as maintenance treatment for patients with platinum-sensitive relapsed ovarian cancer
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-22
    Jonathan A. Ledermann; Eric Pujade-Lauraine

    The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib (Lynparza™) was the first personalized treatment for patients with high-grade serous ovarian cancer, initially receiving regulatory approval in Europe for the treatment of those patients with a germline or somatic BRCA1 or BRCA2 mutation (BRCAm).1

    更新日期:2019-11-18
  • Ratio of carcinoembryonic antigen in pleural fluid and serum for the diagnosis of malignant pleural effusion
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-22
    Klaus Hackner; Peter Errhalt; Sabin Handzhiev

    Malignant pleural effusion (MPE) is a common phenomenon in lung cancer and other cancer-related pleural diseases.1 However, a clear and fast diagnosis is often challenging. The presence of MPE is attributable to an advanced state of disease and a correct diagnosis is crucial for further therapeutic decisions. Furthermore, MPE influences the prognosis of the patients. The median survival with MPE has been reported as 3–12 months, depending on the site of the primary neoplasm.2

    更新日期:2019-11-18
  • Management of metastatic cutaneous melanoma: updates in clinical practice
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-22
    Gustavo Schvartsman; Patricia Taranto; Isabella C. Glitza; Sanjiv S. Agarwala; Michael B. Atkins; Antonio C. Buzaid

    In recent years, we have witnessed great progress in the treatment of patients with metastatic melanoma. Most of the United States Food and Drug Administration (FDA) drug approvals have taken place in the past 7 years. Although metastatic melanoma still remains a frequently fatal disease, a large proportion of patients can now be anticipated to respond to therapy. Furthermore, a significant subset of patients can experience long-term remissions through the application of various treatment approaches.

    更新日期:2019-11-18
  • Therapeutic effects of the novel Leucyl-tRNA synthetase inhibitor BC-LI-0186 in non-small cell lung cancer
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-19
    Eun Young Kim; Jin Gu Lee; Jung Mo Lee; Arum Kim; Hee Chan Yoo; Kibum Kim; Minji Lee; Chulho Lee; Gyoonhee Han; Jung Min Han; Yoon Soo Chang

    Lung cancer is the third most common malignancy and still the leading cause of cancer death in the world. In the United States, it is projected that there may be approximately 222,500 new cases and 155,870 deaths from lung cancer in 2017.1 The development of target agents and immunotherapy has improved treatment outcomes, but ultimate resistance to these therapies requires new approaches to combat carcinogenesis and resistance to current therapies.2

    更新日期:2019-11-18
  • Real-world comparative effectiveness of nab-paclitaxel plus gemcitabine versus FOLFIRINOX in advanced pancreatic cancer: a systematic review
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-19
    Elena Gabriela Chiorean; Winson Y. Cheung; Guido Giordano; George Kim; Salah-Eddin Al-Batran

    Pancreatic cancer is estimated to be the third leading cause of cancer-related mortality in the United States (US).1,2 As has been the case for many years, the projected number of deaths in 2019 (45,750) is expected to nearly equal the number of new cases (56,770).1,2 While the 5-year survival rate for all stages combined is approximately 9% (lowest among all cancers), more than half of all patients diagnosed with pancreatic cancer present with metastatic disease, which carries a 5-year survival rate of approximately 3%.1,2

    更新日期:2019-11-18
  • New frontiers in the medical management of gastrointestinal stromal tumours
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-17
    Alessandro Mazzocca; Andrea Napolitano; Marianna Silletta; Mariella Spalato Ceruso; Daniele Santini; Giuseppe Tonini; Bruno Vincenzi

    Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms, with a global annual incidence of 10–15 cases per million.1–3 GISTs arise from the interstitial cells of Cajal4 primarily in the gastrointestinal (GI) tract, with the majority found in the stomach (60%),3 although extra-GI sites of origin are possible.5,6

    更新日期:2019-11-18
  • Axitinib overcomes multiple imatinib resistant cKIT mutations including the gatekeeper mutation T670I in gastrointestinal stromal tumors
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-17
    Feiyang Liu; Fengming Zou; Cheng Chen; Kailin Yu; Xiaochuan Liu; Shuang Qi; Jiaxin Wu; Chen Hu; Zhenquan Hu; Juan Liu; Xuesong Liu; Li Wang; Juan Ge; Wenchao Wang; Tao Ren; Mingfeng Bai; Yujiao Cai; Xudong Xiao; Feng Qian; Jun Tang; Qingsong Liu; Jing Liu

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Constitutive activation of cKIT kinase mediated signaling pathway is essential for the tumorigenesis of GISTs.1,2 cKIT kinase is a type III receptor tyrosine kinase that upon stem cell factor (SCF) stimulation will activate downstream signaling pathways such as RAS/RAF/ERK and PI3K/AKT to regulate the cell proliferation, survival, apoptosis, and differentiation. Approximately 75% GISTs harbor oncogenic gain-of-function KIT gene mutations that mimic the SCF-induced constitutive signaling pathway activation.3 Currently, over 20 different functional mutations have been identified in the clinic.4 Most primary mutations such as L576P and V559D/A/G mutants occur in the extracellular domain and juxtamembrane (JM) domain.5–7 Secondary mutations are induced by drug treatment and usually located at the ATP binding pocket such as cKIT V654A and the gatekeeper mutant T670I, or at the activation loop such as D816V/H, N822K, and A829P .8–10

    更新日期:2019-11-18
  • Induction of osteoclast-like cell formation by leptin-induced soluble intercellular adhesion molecule secreted from cancer cells
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-14
    Cheng-Fang Tsai; Jia-Hong Chen; Chen-Teng Wu; Pei-Chun Chang; Shu-Lin Wang; Wei-Lan Yeh

    Adipose-tissue-derived molecules, including adipokines, are emerging as pivotal regulators that link obesity with cancer. Accumulating evidence indicates that obesity adversely impacts on cancer treatment and the development of drug resistance, particularly through leptin and the leptin receptor.1–3 Leptin is a tumorigenic adipokine suggested to promote tumorigenesis and therapeutic resistance in many cancers.4 Leptin also shapes the tumor microenvironment to potentiate angiogenesis and metastasis.5 In addition, leptin is associated with the expansion of the cancer stem-cell subpopulations,4,6 and the expression of the leptin receptor is necessary for maintaining its cancer stem-cell-like property.7 It is also reported that leptin upregulates pro-inflammatory cytokines and promotes the immune escape of cancer cells.8 In the past decade, leptin has been largely investigated in hormone-related cancers; however, the role of leptin in other types of cancer is gathering interest.

    更新日期:2019-11-18
  • FAM84B promotes prostate tumorigenesis through a network alteration
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-13
    Yanzhi Jiang; Xiaozeng Lin; Anil Kapoor; Lizhi He; Fengxiang Wei; Yan Gu; Wenjuan Mei; Kuncheng Zhao; Huixiang Yang; Damu Tang

    Prostate cancer (PC) is the most frequently diagnosed male malignancy in the developed world.1 PC evolves from high grade prostatic intra-epithelial neoplasia lesions which may progress to metastasis diseases.2 Primary PCs are managed by a variety of treatment options including active surveillance, surgery, and radiation; treatment choices consider multiple factors such as disease severity, patient age and preference. The severity of PCs is graded using the Gleason score (GS) and GS-based World Health Organization (WHO) PC grading system (WHO grade group 1–5) or its equivalent ISUP (the International Society of Urological Pathology) grade.3–5 Aproximately 30% of tumors will relapse following surgery, evident by an increase in serum prostate-specific antigen (PSA), a process that is known as biochemical recurrence (BCR).6 The recurrence is a major progression of PC, which often results in poor prognosis; a large percentage of relapsed PCs will progress to metastatic disease.7 With a few exceptions, metastases remain incurable. Metastatic PCs are managed with androgen-deprivation therapy, which was based on the seminal discovery of PC proliferation relying on androgen signaling in the 1940s.8,9 Nonetheless, metastatic castration-resistant PC (mCRPC) inevitably occurs.10,11 Although mCRPC can be treated with taxane-based chemotherapy, androgen receptor (AR)-targeting therapy involving either abiraterone or enzalutamide,11–13 and immunotherapy,14,15 these treatments offer modest benefits in these patients.11,16 The progression of PC is regulated by complex networks, of which our understanding remains limited.

    更新日期:2019-11-18
  • Pressurized intraperitoneal aerosol chemotherapy with low-dose cisplatin and doxorubicin (PIPAC C/D) in patients with gastric cancer and peritoneal metastasis: a phase II study
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-13
    Florian Struller; Philipp Horvath; Wiebke Solass; Frank-Jürgen Weinreich; Dirk Strumberg; Marios K. Kokkalis; Imma Fischer; Christoph Meisner; Alfred Königsrainer; Marc A. Reymond

    Gastric cancer is the fifth most common cancer worldwide and associated with a poor prognosis and about 740,000 deaths per year.1,2 The 5-year overall survival is around 25% but varies greatly depending on the tumor stage (TNM) and histology. In particular, signet-ring histology is associated with dismal prognosis.3 Surgery with lymph node dissection is the primary treatment for medically fit patients with resectable tumors.4 Perioperative chemotherapy is recommended following curative (R0) resection. The recurrence rate is high after frontline multimodal therapy for 40–80% of the patients.5,6 The median survival of patients with unresectable gastric cancer treated with systemic chemotherapy is not greater than 12 months.7 Among such patients, the median survival of those with peritoneal metastasis (PM) was reported to be even worse at 6–10 months.8 Therefore, National Comprehensive Cancer Network Guidelines for Gastric Cancer encourages patients with gastric cancer to participate in well-designed clinical trials investigating novel therapeutic strategies to enable further advances.4

    更新日期:2019-11-18
  • Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in patients with metastatic melanoma?
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-13
    Lorena Incorvaia; Giuseppe Badalamenti; Gaetana Rinaldi; Juan Lucio Iovanna; Daniel Olive; Mirna Swayden; Lidia Terruso; Bruno Vincenzi; Fabio Fulfaro; Viviana Bazan; Antonio Russo; Daniele Fanale

    Melanoma is the most aggressive form of skin cancer, causing more than 70% of skin cancer-related deaths and accounting for 3% of new cancer cases estimated in Italy (http://www.registri-tumori.it). According to the Italian Cancer Society, an annual average incidence of 12.5 new melanoma diagnoses per 100,000 males and 13.1 per 100,000 females were registered.1 It is considered to be the second most frequent neoplasm in youth, with global incidence rates continuously increasing over the last few decades, resulting in a poor prognosis with an extremely low 5-year survival rate in the case of metastatic tumors.2,3 Cutaneous melanoma can be divided into four major subtypes: nodular melanoma, superficial spreading, lentigo maligna melanoma (LMM), and acral lentiginous.4 The melanoma onset is caused by complex interactions between genetic, phenotypic, and environmental factors.5,6 Melanomas have been shown to be genetically and phenotypically heterogeneous tumors harboring different genetic alterations in three main oncogenes: BRAF, NRAS, and c-KIT.7 Large-scale analysis of melanoma exome data discovered six novel melanoma genes (PPP6C, RAC1, SNX31, TACC1, STK19, and ARID2), three of which, RAC1, PPP6C, and STK19, harbored potentially targetable mutations. Moreover, RB and p53 pathways are deregulated in this type of malignancy.8 Mutations in genes encoding the SWI/SNF chromatin-remodeling enzymes such as ARID1A (BAF250A/SMARCF1), ARID1B (BAF250B), ARID2 (BAF200), and SMARCA4 (BRG1) are involved in melanoma, in addition to other chromatin organization/histone modification proteins (EZH1,EZH2,SETD2, and TRRAP).8

    更新日期:2019-11-18
  • Palbociclib and ribociclib in breast cancer: consensus workshop on the management of concomitant medication
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-10
    Meritxell Bellet; Faten Ahmad; Rafael Villanueva; Carolina Valdivia; Julián Palomino-Doza; Ada Ruiz; Xavier Gonzàlez; Encarna Adrover; Analía Azaro; Maria Valls-Margarit; Josep Lluís Parra; Juan Aguilar; Maria Vidal; Anastasi Martín; Joaquín Gavilá; Santiago Escrivá-de-Romaní; Antonia Perelló; Cristina Hernando; Ainhara Lahuerta; Pilar Zamora; Victoria Reyes; María Alcalde; Helena Masanas; Pamela Céliz; Isabel Ruíz; Miguel Gil; Miguel Àngel Seguí; Lorena de la Peña

    In the ‘First Workshop on Pharmacology and Management of Cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6i): Consensus about Concomitant Medications’, promoted by the Spanish Breast Cancer Cooperative Group SOLTI, medical oncologists specialized in breast cancer joined physicians specialized in pharmacology, cardiology, psychiatry, infectious diseases, palliative care or radiation oncology in an interdisciplinary discussion forum, at Spanish national level, to address different issues regarding patients treated with palbociclib and ribociclib. These issues included overall management of adverse events (AEs) of special interest, expert opinion about clinical situations for which evidence of treatment with these drugs is limited, and, above all, concomitant medications that may be safely administered. This workshop was held on 22 May 2018. This article brings together the issues that were addressed, the information compiled and the conclusions of this 1-day meeting.

    更新日期:2019-11-18
  • Proteomic analysis of gemcitabine-resistant pancreatic cancer cells reveals that microtubule-associated protein 2 upregulation associates with taxane treatment
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-10
    Tessa Ya Sung Le Large; Btissame El Hassouni; Niccola Funel; Bart Kok; Sander R. Piersma; Thang V. Pham; Kenneth P. Olive; Geert Kazemier; Hanneke W.M. van Laarhoven; Connie R. Jimenez; Maarten F. Bijlsma; Elisa Giovannetti

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by a high lethality, with only 7% of patients alive 5 years after diagnosis.1 Most patients present with advanced disease stages, either locally advanced (stage III) or with distant metastases (stage IV), leaving palliative chemotherapy as the only therapeutic option.2 Aggressive multimodal therapy offers the best survival chances for patients diagnosed with early stage disease (stage I–IIb).3 This treatment consists of a combination of resection followed by adjuvant chemotherapy. Currently, standard adjuvant therapy consists of six cycles of gemcitabine improving disease-free survival (DFS) from 6.7 to 13.4 months.3,4

    更新日期:2019-11-18
  • Intensive first-line FIr-C/FOx-C association of triplet chemotherapy plus cetuximab in RAS wild-type metastatic colorectal cancer patients: preliminary phase II data and prediction of individual limiting toxicity syndromes by pharmacogenomic biomarkers
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-10
    Gemma Bruera; Silvia Massacese; Francesco Pepe; Umberto Malapelle; Antonella Dal Mas; Eugenio Ciacco; Giuseppe Calvisi; Giancarlo Troncone; Maurizio Simmaco; Enrico Ricevuto

    Therapeutic strategy of metastatic colorectal cancer (MCRC) is planned by predictive/prognostic biomarkers and the patients’ fitness for selected targeted drugs, antivascular endothelial growth factor (anti-VEGF) or anti-epidermal growth factor receptor (anti-EGFR), associated with doublet or more intensive triplet chemotherapy, properly weighing the expected clinical outcome with toxicity in individual patients.1

    更新日期:2019-11-18
  • Diagnostic and therapeutic potential of the gut microbiota in patients with early hepatocellular carcinoma
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-10
    Francesca Romana Ponziani; Alberto Nicoletti; Antonio Gasbarrini; Maurizio Pompili

    Hepatocellular carcinoma (HCC) is a heterogeneous tumor usually arising in an inflammatory environment. Indeed, in the vast majority of cases, HCC is diagnosed in patients with chronic liver disease, in whom it represents one of the leading causes of death despite surveillance programs for early diagnosis.1 Liver cirrhosis is the paradigm of inflammatory diseases, as it frequently develops in association with chronic viral or alcohol-related hepatitis, or in patients with nonalcoholic fatty liver disease (NAFLD); the hepatocellular damage produced by various etiologic agents eventually results in tissue repair up to the development of fibrosis. Persistent hepatocellular proliferation in this inflammatory microenvironment promotes genetic mutations that trigger hepatocarcinogenesis.2

    更新日期:2019-11-18
  • Cotargeting Plk1 and androgen receptor enhances the therapeutic sensitivity of paclitaxel-resistant prostate cancer
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-08
    Sol-Bi Shin; Sang-Uk Woo; Hyungshin Yim

    Antimitotic therapies targeting microtubule dynamics, such as vinca alkaloids and taxanes, are widely used for the treatment of cancer.1–4 Taxanes are still the first choice of treatment for several solid malignant tumors, and taxanes in combination with other chemotherapy agents are standard in patients with advanced prostate cancer,5,6 breast cancer,7 ovarian cancer,3 and non-small cell lung cancer.4 Despite the clinical success of taxanes, they still have limitations, such as the acquisition of resistance and dose-dependent toxicity.1,8,9 Acquired taxane resistance is a serious clinical obstacle in effectively treating cancer patients. High expression levels of ABCB1, also known as p-glycoprotein or multidrug resistance protein 1 (MDR1), and multidrug resistance-associated protein 1 (MRP1; ABCC1) are thought to be one of the causes of paclitaxel resistance.8,10 To reduce these limitations, combination chemotherapy has been broadly investigated via in vitro experiments, in vivo studies, and clinical trials. The use of new antimitotic drugs as targeted therapies can offer the possibility to overcome some of the limitations of current antimitotic drugs.

    更新日期:2019-11-18
  • Adjuvant therapy for pancreatic body or tail adenocarcinoma: a study of the National Cancer Database
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-05-03
    Max Seaton; Andrew Hanna; Cherif Boutros; Nader Hanna

    Pancreatic cancer is the fourth leading cause of cancer death among men and women in the US, and will result in an estimated 44,330 deaths in 2018.1 The optimal multimodality therapy for resectable pancreatic ductal adenocarcinoma (PDAC) is controversial.2 Several clinical trials support the use of adjuvant chemotherapy,3–6 while other trials support the use of adjuvant chemoradiation.7–10 Due to a lack of definitive data, current National Comprehensive Cancer Network (NCCN) guidelines recommend either adjuvant chemotherapy alone or adjuvant induction chemotherapy followed by chemoradiation with or without subsequent chemotherapy.11 The adjuvant regimen that includes chemoradiation is recommended for patients with high-risk features, such as positive resection margins or positive lymph nodes.11

    更新日期:2019-11-18
  • Gelsolin-like actin-capping protein has prognostic value and promotes tumorigenesis and epithelial-mesenchymal transition via the Hippo signaling pathway in human bladder cancer
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-04-29
    Lyu Zhaojie; Liu Yuchen; Chen Miao; Chen Yacun; Wu Shayi; He Anbang; Liao Xinhui; Zhang Meng; Wu Peipei; Mei Hongbing; Wang Feng; Cai Zhiming; Guan Xinyuan

    Bladder cancer is the fourth most common cancer in men and one of the most significant causes of cancer-related death worldwide, with transitional cell carcinoma (TCC) being the predominant form (representing 90% of cases).1,2 The superficial or nonmuscle-invasive TCCs, which could be managed by transurethral resection, tend to recur or progress.3 The advanced or muscle-invasive TCCs are associated with a high risk of death from distant metastases.4 Because of the lack of suitable diagnostic biomarkers and effective therapies, patients are often diagnosed at advanced stages and the mortality rate keeps increasing.5 Considering these issues, it is essential to study TCCs at the genetic level to characterize the targeted agents.

    更新日期:2019-11-18
  • Harnessing immunotherapy for liver recipients with hepatocellular carcinoma: a review from a transplant oncology perspective
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-04-26
    Cheng-Maw Ho; Hui-Ling Chen; Rey-Heng Hu; Po-Huang Lee

    The management of hepatocellular carcinoma (HCC) recurrence after liver transplantation is an unmet need in therapeutics. This is because under immunosuppression, cancer develops early during the post-transplant period and has a higher chance of extrahepatic spreading, particularly if the pretransplant HCC status exceeds Milan or University of California San Francisco criteria.1–3 In this scenario, locoregional therapy, which is the first-line therapeutic choice for recurrent HCC in nontransplant patients, may be ineffective; thus, effective management strategies are urgently required.4 In liver recipients with disseminated HCC recurrence, sorafenib confers survival benefits but is associated with considerable drug toxicity.5 Most immunotherapies for organ transplantation are intended to achieve sufficient immunosuppression to prevent organ rejection or limit autoreactivity without impairing the host’s ability to protect against opportunistic infections and malignancies. Thus, patients with new or recurrent malignancies after transplantation often have a relatively low chance of undergoing another surgery; however, in these patients, the effects of other treatment approaches may be nonsignificant.6 The development of systemic therapy with sustained effectiveness is required urgently.

    更新日期:2019-11-18
  • LKB1 and YAP phosphorylation play important roles in Celastrol-induced β-catenin degradation in colorectal cancer
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-04-22
    Shuren Wang; Kai Ma; Cuiqi Zhou; Yu Wang; Guanghui Hu; Lechuang Chen; Zhuo Li; Chenfei Hu; Qing Xu; Hongxia Zhu; Mei Liu; Ningzhi Xu

    As the most common gastrointestinal (GI) tract cancer worldwide, colorectal cancer (CRC) represents the fifth leading causes of cancer deaths among both men and women.1 CRC acquires many genetic alterations, and some signaling pathways involved are clearly singled out as key factors in tumor formation. Activation of the Wnt pathway is regarded as the initiating event in CRC.2 The core of Wnt signaling is β-catenin, which is regulated by a cytoplasmic destruction complex consisting of a central scaffold protein Axin, adenomatous polyposis coli (APC), glycogen synthase kinase 3β (GSK-3β), and casein kinase 1 (CK1).3 As an critical transcriptional co-activator of the Wnt pathway, β-catenin regulates target gene expression.4 Aberrant expression of β-catenin induces malignant transformation of normal cells, and its abnormal activity has been reported in many cancer types.

    更新日期:2019-11-18
  • Adjuvant chemotherapy improves prognosis of resectable stage IV colorectal cancer: a comparative study using inverse probability of treatment weighting
    Ther. Adv. Med. Oncol. (IF 5.670) Pub Date : 2019-04-16
    Hiroaki Nozawa; Hirotoshi Takiyama; Kiyoshi Hasegawa; Kazushige Kawai; Keisuke Hata; Toshiaki Tanaka; Takeshi Nishikawa; Kazuhito Sasaki; Manabu Kaneko; Koji Murono; Shigenobu Emoto; Hirofumi Sonoda; Jun Nakajima

    Multimodality treatment has been the basic tenet in the treatment of advanced colorectal cancer (CRC) with the aim of improving prognoses.1 In addition to complete surgical resection, adjuvant chemotherapy (AC) in resected CRC has been attracting increasing interest. Previous clinical trials showed that 5-fluorouracil (5-FU) based AC was effective for reducing recurrence and thereby contributed to longer overall survival (OS) in patients with stage III CRC.2–6 Moreover, oxaliplatin-including AC further improved the long-term prognosis of stage III colon patients.7–9 However, the efficacy of AC after curative resection for stage IV CRC has been debated, with conflicting reports of benefits. Several randomized trials on 5-FU-based AC failed to demonstrate any survival benefit in CRC patients who underwent the resection of liver metastases after curative resection.10–12 On the other hand, a recent phase III randomized controlled trial (RCT) showed that oral tegafur/uracil and leucovorin significantly prolonged recurrence-free survival (RFS) in CRC patients with synchronous or metachronous liver-limited metastases after primary resection and hepatectomy.13 However, the trial did not prove an OS benefit by oral AC in this patient cohort.13 Moreover, the efficacy of AC after curative resection for CRC with synchronous metastases in various organs remains unclear because of the paucity of systematic studies.

    更新日期:2019-11-18
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