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  • Targeted therapies: Survival ENDEAVORs
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 
    Lisa Hutchinson

    Targeted therapies: Survival ENDEAVORs Nature Reviews Clinical Oncology, Published online: 19 September 2017; doi:10.1038/nrclinonc.2017.155

    更新日期:2017-09-20
  • Chimeric antigen receptor T-cell therapy — assessment and management of toxicities
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-09-19
    Sattva S. Neelapu, Sudhakar Tummala, Partow Kebriaei, William Wierda, Cristina Gutierrez, Frederick L. Locke, Krishna V. Komanduri, Yi Lin, Nitin Jain, Naval Daver, Jason Westin, Alison M. Gulbis, Monica E. Loghin, John F. de Groot, Sherry Adkins, Suzanne E. Davis, Katayoun Rezvani, Patrick Hwu, Elizabeth J. Shpall

    Immunotherapy using T cells genetically engineered to express a chimeric antigen receptor (CAR) is rapidly emerging as a promising new treatment for haematological and non-haematological malignancies. CAR-T-cell therapy can induce rapid and durable clinical responses, but is associated with unique acute toxicities, which can be severe or even fatal. Cytokine-release syndrome (CRS), the most commonly observed toxicity, can range in severity from low-grade constitutional symptoms to a high-grade syndrome associated with life-threatening multiorgan dysfunction; rarely, severe CRS can evolve into fulminant haemophagocytic lymphohistiocytosis (HLH). Neurotoxicity, termed CAR-T-cell-related encephalopathy syndrome (CRES), is the second most-common adverse event, and can occur concurrently with or after CRS. Intensive monitoring and prompt management of toxicities is essential to minimize the morbidity and mortality associated with this potentially curative therapeutic approach; however, algorithms for accurate and consistent grading and management of the toxicities are lacking. To address this unmet need, we formed a CAR-T-cell-therapy-associated TOXicity (CARTOX) Working Group, comprising investigators from multiple institutions and medical disciplines who have experience in treating patients with various CAR-T-cell therapy products. Herein, we describe the multidisciplinary approach adopted at our institutions, and provide recommendations for monitoring, grading, and managing the acute toxicities that can occur in patients treated with CAR-T-cell therapy.

    更新日期:2017-09-20
  • Immunotherapy: Shining light on immune-based mechanisms
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 
    Lisa Hutchinson

    Immunotherapy: Shining light on immune-based mechanisms Nature Reviews Clinical Oncology, Published online: 19 September 2017; doi:10.1038/nrclinonc.2017.152

    更新日期:2017-09-20
  • Colorectal cancer: Liquid biopsy provides highly sensitive detection of RAS mutations
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 
    Peter Sidaway

    Colorectal cancer: Liquid biopsy provides highly sensitive detection of RAS mutations Nature Reviews Clinical Oncology, Published online: 19 September 2017; doi:10.1038/nrclinonc.2017.154

    更新日期:2017-09-20
  • Radiotherapy: Importantly, less is effective
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 
    Diana Romero

    Radiotherapy: Importantly, less is effective Nature Reviews Clinical Oncology, Published online: 12 September 2017; doi:10.1038/nrclinonc.2017.139

    更新日期:2017-09-19
  • Immunotherapy: Cancer vaccines on the move
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-09-12
    Jacques Banchereau, Karolina Palucka

    Immunotherapy: Cancer vaccines on the move Nature Reviews Clinical Oncology, Published online: 12 September 2017; doi:10.1038/nrclinonc.2017.149 The development of therapeutic cancer vaccines has been pursued for many decades. Many vaccines can elicit immunity to tumour antigens, although their clinical efficacy remains modest. Recent results from two clinical trials highlight the potential of personalized vaccination strategies, made possible by high-throughput approaches to the identification of immunogenic tumour neoantigens. Thus, therapeutic cancer vaccines might soon move into the mainstream.

    更新日期:2017-09-19
  • Corrigendum: Can we deliver randomized trials of focal therapy in prostate cancer?
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 
    Hashim U. Ahmed, Viktor Berge, David Bottomley, William Cross, Rakesh Heer, Richard Kaplan, Tom Leslie, Chris Parker, Clare Relton, Richard Stephens, Matthew R. Sydes, Lindsay Turnbull, Jan van der Meulen, Andrew Vickers, Timothy Wilt, Mark Emberton, and the Prostate Cancer RCT Consensus Group

    Corrigendum: Can we deliver randomized trials of focal therapy in prostate cancer? Nature Reviews Clinical Oncology, Published online: 12 September 2017; doi:10.1038/nrclinonc.2017.86

    更新日期:2017-09-19
  • Manifesto for global women's health
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-09-12
    Ophira Ginsburg

    Manifesto for global women's health Nature Reviews Clinical Oncology, Published online: 12 September 2017; doi:10.1038/nrclinonc.2017.150 Women's health is more than reproductive health. Why does this phrase still need to be repeated? This commentary highlights the urgent need to encourage more women to lead, research, and educate to move beyond stereotypes and to ensure we push forward in improving the lives of women everywhere.

    更新日期:2017-09-19
  • Breast cancer: Short-term NAT reveals resistance
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 
    David Killock

    Breast cancer: Short-term NAT reveals resistance Nature Reviews Clinical Oncology, Published online: 5 September 2017; doi:10.1038/nrclinonc.2017.143

    更新日期:2017-09-19
  • Brain cancer: Temozolomide improves outcomes
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 
    Peter Sidaway

    Brain cancer: Temozolomide improves outcomes Nature Reviews Clinical Oncology, Published online: 31 August 2017; doi:10.1038/nrclinonc.2017.145

    更新日期:2017-09-19
  • Breast cancer: AKT inhibition effective against TNBC
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 
    Peter Sidaway

    Breast cancer: AKT inhibition effective against TNBC Nature Reviews Clinical Oncology, Published online: 31 August 2017; doi:10.1038/nrclinonc.2017.147

    更新日期:2017-09-19
  • Chimeric antigen receptor T-cell therapies for lymphoma
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-08-31
    Jennifer N. Brudno, James N. Kochenderfer

    New therapies are needed for patients with Hodgkin or non-Hodgkin lymphomas that are resistant to standard therapies. Indeed, unresponsiveness to standard chemotherapy and relapse after autologous stem-cell transplantation are indicators of an especially poor prognosis. Chimeric antigen receptor (CAR) T cells are emerging as a novel treatment modality for these patients. Clinical trial data have demonstrated the potent activity of anti-CD19 CAR T cells against multiple subtypes of B-cell lymphoma, including diffuse large-B-cell lymphoma (DLBCL), follicular lymphoma, mantle-cell lymphoma, and marginal-zone lymphoma. Importantly, anti-CD19 CAR T cells have impressive activity against chemotherapy-refractory lymphoma, inducing durable complete remissions lasting >2 years in some patients with refractory DLBCL. CAR-T-cell therapies are, however, associated with potentially fatal toxicities, including cytokine-release syndrome and neurological toxicities. CAR T cells with novel target antigens, including CD20, CD22, and κ-light chain for B-cell lymphomas, and CD30 for Hodgkin and T-cell lymphomas, are currently being investigated in clinical trials. Centrally manufactured CAR T cells are also being tested in industry-sponsored multicentre clinical trials, and will probably soon become a standard therapy. Herein, we review the clinical efficacy and toxicity of CAR-T-cell therapies for lymphoma, and discuss their limitations and future directions with regard to toxicity management, CAR designs and CAR-T-cell phenotypes, conditioning regimens, and combination therapies.

    更新日期:2017-09-19
  • Health policy: Me-too drugs with limited benefits — the tale of regorafenib for HCC
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-07-18
    Bishal Gyawali, Vinay Prasad

    Regorafenib is only the second agent approved by the FDA for the treatment of patients with advanced-stage hepatocellular carcinoma. Herein, we discuss the evidence that led to the approval of this agent. Examination of this process reveals important challenges associated with drug regulation, relating to trial design, treatment toxicity, and real-world clinical benefit.

    更新日期:2017-09-06
  • Prostate cancer: A new standard-of-care for advanced-stage disease
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-08-08
    Anis A. Hamid, Christopher J. Sweeney

    First-line, potent androgen blockade for patients with newly diagnosed, advanced-stage, castration-sensitive prostate cancer is confirmed as an effective strategy by data from the STAMPEDE and LATITUDE trials. Herein, we highlight the benefits, discuss caveats and consider the clinical care implications of these findings.

    更新日期:2017-09-06
  • Sarcoma: Does histotype-tailored neoadjuvant therapy improve outcomes?
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-08-08
    Robin L. Jones, Khin Thway

    Patients with metastatic soft-tissue sarcoma can benefit from systemic therapy, but the best drug combinations for the different disease subtypes remain to be established. Recently, great emphasis has been placed on histology-based chemotherapy regimens. Herein, we discuss the results of a recently published study demonstrating that some of these regimens are not superior to standard-of-care chemotherapy in the neoadjuvant setting.

    更新日期:2017-09-06
  • Genetics: Taking single-cell transcriptomics to the bedside
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-08-01
    Sam Behjati, Muzlifah Haniffa

    Important biological questions can be addressed by interrogating the transcriptomes of cancer cells. In a recently published landmark study, Giustacchini and collaborators used a single-cell approach to analyse mRNA of cancer cells derived from patients with chronic myeloid leukaemia. Herein, we discuss how this approach could be used to address relevant clinical questions.

    更新日期:2017-09-06
  • Breast cancer: What lies beyond APHINITY for HER2-positive breast cancer?
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-08-08
    Sasha E. Stanton, Nancy E. Davidson

    Potential strategies for improving the outcomes of patients with early stage HER2-positive (HER2+) breast cancer have included dual anti-HER2 therapy. Recent results from the APHINITY trial show a statistically significant, but clinically modest, benefit from the addition of pertuzumab to trastuzumab and chemotherapy. Subsequent trials should focus on biomarkers to identify patients with HER2+ breast cancer who require more-intensive or less-intensive therapy.

    更新日期:2017-09-06
  • Breast cancer: T-DM1 — an important agent in the history of breast cancer management
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-08-08
    Otto Metzger-Filho, Eric P. Winer

    Updated results from the EMILIA and TH3RESA trials in patients with advanced-stage HER2-positive breast cancer confirm the overall survival benefit and favourable safety profile of T-DM1 after prolonged follow-up durations. The efficacy of T-DM1 as a second or later line of treatment indicates that HER2 is a relevant therapeutic target throughout the course of the disease.

    更新日期:2017-09-06
  • The immune contexture in cancer prognosis and treatment
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-07-25
    Wolf H. Fridman, Laurence Zitvogel, Catherine Sautès–Fridman, Guido Kroemer

    Immunotherapy is currently the most rapidly advancing area of clinical oncology, and provides the unprecedented opportunity to effectively treat, and even cure, several previously untreatable malignancies. A growing awareness exists of the fact that the success of chemotherapy and radiotherapy, in which the patient's disease can be stabilized well beyond discontinuation of treatment (and occasionally is cured), also relies on the induction of a durable anticancer immune response. Indeed, the local immune infiltrate undergoes dynamic changes that accompany a shift from a pre-existing immune response to a therapy-induced immune response. As a result, the immune contexture, which is determined by the density, composition, functional state and organization of the leukocyte infiltrate of the tumour, can yield information that is relevant to prognosis, prediction of a treatment response and various other pharmacodynamic parameters. Several complementary technologies can be used to explore the immune contexture of tumours, and to derive biomarkers that could enable the adaptation of individual treatment approaches for each patient, as well as monitoring a response to anticancer therapies.

    更新日期:2017-09-06
  • Fusions in solid tumours: diagnostic strategies, targeted therapy, and acquired resistance
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-08-31
    Alison M. Schram, Matthew T. Chang, Philip Jonsson, Alexander Drilon

    Structural gene rearrangements resulting in gene fusions are frequent events in solid tumours. The identification of certain activating fusions can aid in the diagnosis and effective treatment of patients with tumours harbouring these alterations. Advances in the techniques used to identify fusions have enabled physicians to detect these alterations in the clinic. Targeted therapies directed at constitutively activated oncogenic tyrosine kinases have proven remarkably effective against cancers with fusions involving ALK, ROS1, or PDGFB, and the efficacy of this approach continues to be explored in malignancies with RET, NTRK1/2/3, FGFR1/2/3, and BRAF/CRAF fusions. Nevertheless, prolonged treatment with such tyrosine-kinase inhibitors (TKIs) leads to the development of acquired resistance to therapy. This resistance can be mediated by mutations that alter drug binding, or by the activation of bypass pathways. Second-generation and third-generation TKIs have been developed to overcome resistance, and have variable levels of activity against tumours harbouring individual mutations that confer resistance to first-generation TKIs. The rational sequential administration of different inhibitors is emerging as a new treatment paradigm for patients with tumours that retain continued dependency on the downstream kinase of interest.

    更新日期:2017-09-06
  • EMT, CSCs, and drug resistance: the mechanistic link and clinical implications
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-04-11
    Tsukasa Shibue, Robert A. Weinberg

    The success of anticancer therapy is usually limited by the development of drug resistance. Such acquired resistance is driven, in part, by intratumoural heterogeneity — that is, the phenotypic diversity of cancer cells co-inhabiting a single tumour mass. The introduction of the cancer stem cell (CSC) concept, which posits the presence of minor subpopulations of CSCs that are uniquely capable of seeding new tumours, has provided a framework for understanding one dimension of intratumoural heterogeneity. This concept, taken together with the identification of the epithelial-to-mesenchymal transition (EMT) programme as a critical regulator of the CSC phenotype, offers an opportunity to investigate the nature of intratumoural heterogeneity and a possible mechanistic basis for anticancer drug resistance. In fact, accumulating evidence indicates that conventional therapies often fail to eradicate carcinoma cells that have entered the CSC state via activation of the EMT programme, thereby permitting CSC-mediated clinical relapse. In this Review, we summarize our current understanding of the link between the EMT programme and the CSC state, and also discuss how this knowledge can contribute to improvements in clinical practice.

    更新日期:2017-09-06
  • Clinical utility of gene-expression signatures in early stage breast cancer
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-05-31
    Maryann Kwa, Andreas Makris, Francisco J. Esteva

    Breast cancer is a heterogeneous disease, with different subtypes having a distinct biological, molecular, and clinical course. Assessments of standard clinical and pathological features have traditionally been used to determine the use of adjuvant systemic therapy in patients with early stage breast cancer; however, the ability to identify those who will benefit from adjuvant chemotherapy remains a challenge, leading to the overtreatment of some patients. Advances in molecular medicine have substantially improved the accuracy of gene-expression profiling of breast tumours, resulting in improvements in the ability to predict a patient's risk of breast cancer recurrence and likely response to endocrine therapy and/or chemotherapy. These genomic assays, several of which are commercially available, have aided physicians in tailoring treatment decisions for patients at the individual level. Herein, we describe the available data on the clinical validity of the most widely available assays in patients with early stage breast cancer, with a focus on the development, validation, and clinical application of these assays, in addition to the anticipated outcomes of ongoing prospective trials. We also review data from comparative studies of these assays and from cost-effectiveness analyses relating to their clinical use.

    更新日期:2017-09-06
  • Monitoring immune-checkpoint blockade: response evaluation and biomarker development
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-06-27
    Mizuki Nishino, Nikhil H. Ramaiya, Hiroto Hatabu, F. Stephen Hodi

    Cancer immunotherapy using immune-checkpoint blockade (ICB) has created a paradigm shift in the treatment of advanced-stage cancers. The promising antitumour activity of monoclonal antibodies targeting the immune-checkpoint proteins CTLA-4, PD-1, and PD-L1 led to regulatory approvals of these agents for the treatment of a variety of malignancies. Patients might experience clinical benefits from treatment with these agents, despite unconventional patterns of tumour response that can be misinterpreted as disease progression, warranting a new, specific approach to evaluate responses to immunotherapy. In addition, biomarkers that can predict responsiveness to ICB are being extensively investigated to further advance precision immunotherapy. Herein, we review the biological mechanisms underlying the unconventional response patterns associated with ICB, describe strategies for the objective assessments of such responses, and also highlight the ongoing efforts to identify biomarkers, in order to guide treatment with ICB. We provide state-of-the-art knowledge of immune-related response evaluations, identify unmet needs requiring further investigations, and propose future directions to maximize the benefits of ICB therapy.

    更新日期:2017-09-06
  • Antibody–drug conjugates in glioblastoma therapy: the right drugs to the right cells
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-07-04
    Hui K. Gan, Martin van den Bent, Andrew B. Lassman, David A. Reardon, Andrew M. Scott

    Glioblastomas are high-grade brain tumours with a poor prognosis and, currently, few available therapeutic options. This lack of effective treatments has been linked to diverse factors, including target selection, tumour heterogeneity and poor penetrance of therapeutic agents through the blood–brain barrier and into tumours. Therapies using monoclonal antibodies, alone or linked to cytotoxic payloads, have proved beneficial for patients with different solid tumours; these approaches are currently being explored in patients with glioblastoma. In this Review, we summarise clinical data regarding antibody–drug conjugates (ADCs) against a variety of targets in glioblastoma, and compare the efficacy and toxicity of targeting EGFR with ADCs versus naked antibodies in order to illustrate key aspects of the use of ADCs in this malignancy. Finally, we discuss the complex challenges related to the biology and mutational changes of glioblastoma that can affect the use of ADC-based therapies in patients with this disease, and highlight potential strategies to improve efficacy.

    更新日期:2017-09-06
  • HER2-positive breast cancer is lost in translation: time for patient-centered research
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-08-01
    Isabelle Gingras, Géraldine Gebhart, Evandro de Azambuja, Martine Piccart-Gebhart

    No biomarker beyond HER2 itself, which suffers from a low positive predictive value, has demonstrated clinical utility in breast cancer, despite numerous attempts to improve treatment tailoring for the growing number of anti-HER2 targeted therapies. This prompted us to examine the body of evidence, using a systematic approach, to identify putative predictive biomarkers in HER2-positive breast cancer, and discuss the hitherto failure to address the needs of patients. In the future, it is hoped immune-based biomarkers will predict benefit from anti-HER2 treatments in the neoadjuvant and adjuvant settings. In advanced-stage disease, the quantification of tumour heterogeneity using molecular-imaging technology has generated informative data on the success or failure of the antibody-drug conjugate T-DM1. Treatment tailoring remains a high priority, in cost-constrained health-care systems, but such tailoring will require a dramatic shift in the way translational research is being conducted, with the establishment of large, easily accessible, and well-annotated databases of candidate predictive biomarkers. Single-centre biomarker research should become a thing of the past.

    更新日期:2017-09-06
  • Precision medicine based on epigenomics: the paradigm of carcinoma of unknown primary
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-07-04
    Sebastián Moran, Anna Martinez-Cardús, Stergios Boussios, Manel Esteller

    Epigenetic alterations are a common hallmark of human cancer. Single epigenetic markers are starting to be incorporated into clinical practice; however, the translational use of these biomarkers has not been validated at the 'omics' level. The identification of the tissue of origin in patients with cancer of unknown primary (CUP) is an example of how epigenomics can be incorporated in clinical settings, addressing an unmet need in the diagnostic and clinical management of these patients. Despite the great diagnostic advances made in the past decade, the use of traditional diagnostic procedures only enables the tissue of origin to be determined in ~30% of patients with CUP. Thus, development of molecularly guided diagnostic strategies has emerged to complement traditional procedures, thereby improving the clinical management of patients with CUP. In this Review, we present the latest data on strategies using epigenetics and other molecular biomarkers to guide therapeutic decisions involving patients with CUP, and we highlight areas warranting further research to engage the medical community in this unmet need.

    更新日期:2017-09-06
  • Evolution of lymphoma staging and response evaluation: current limitations and future directions
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-06-13
    Joel Cunningham, Sunil Iyengar, Bhupinder Sharma

    Accurate detection and monitoring of treatment responses is an essential element of the management of patients with lymphoma. In this Perspectives, the authors describe the evolution of lymphoma staging criteria and highlight unaddressed questions, which, if answered, will substantially improve the management of patients with lymphoma.

    更新日期:2017-09-06
  • Evolution and cancer medicine — transformative insights
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-08-22
    Erik Sahai, Charles Swanton

    Few clinical trials incorporate studies of evolutionary cancer biology, despite the frequent emergence of acquired resistance to anticancer therapies. This problem motivated the first CRUK Marshall Symposium on Cancer Evolution in May 2017, which provided a forum for evolutionary and ecological theorists, cancer biologists, and clinicians to consider how evolutionary biology might inform improvements in cancer medicine. Herein, we discuss the key themes and opportunities for the future.

    更新日期:2017-09-06
  • Context: the grey matter of cancer
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-08-22

    As the ESMO conference approaches, we pause to reflect on the latest progress, key challenges, and future directions in clinical oncology. What has the plethora of research and clinical trial data from thousands of publications taught us? That context is paramount. Our ability to understand

    更新日期:2017-08-22
  • Genetics: Conditional selection determines the pathways of cancer evolution
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-08-22
    David Killock

    Mutational profiling is increasingly performed to identify oncogenic alterations that can be matched to particular molecularly targeted drugs. This 'precision medicine' paradigm has resulted in improved outcomes for patients with specific molecular cancer subtypes, but the efficacy of many targeted therapies has been underwhelming. New

    更新日期:2017-08-22
  • Melanoma: Neadjuvant BRAF inhibition enables resection
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-07-11
    Peter Sidaway

    Data from a consecutive series of 13 patients with stage III malignant melanoma indicate that patients with BRAFV600E-mutant marginally resectable or irresectable melanoma are able to derive clinical benefit from neoadjuvant BRAF inhibition. This approach enabled all patients to undergo surgical resection, which

    更新日期:2017-08-22
  • Targeted therapy: ctDNA identified in patients with CUP
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-07-11
    Peter Sidaway

    A next-generation sequencing analysis of circulating tumour DNA (ctDNA) from 442 patients with cancer of unknown primary (CUP) has revealed the presence of at least one detectable alteration in 79.9% of patients, of which 89.6% of alterations were potentially targetable through off-label use of FDA-approved

    更新日期:2017-08-22
  • Genetics: BRCA-mutant breast/ovarian cancer revealed
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-07-11
    Peter Sidaway

    The findings of a large prospective cohort study involving 9,856 women with BRCA1 or BRCA2 mutations indicate a 72% cumulative lifetime risk of breast cancer in those harbouring a BRCA1 mutation and a 69% risk for those harbouring a BRCA2 mutation.

    更新日期:2017-08-22
  • Gastrointestinal cancer: Establishing a family tree
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-07-25
    Diana Romero

    A key question in the study of cancer metastasis is whether distant lesions always originate from lymph-node foci. The results of a study conducted by Kamila Naxerova and colleagues now indicate that this is not always the case for patients with colorectal cancer.Naxerova describes

    更新日期:2017-08-22
  • Haematological cancer: Low-dose CAR T cells are safe and effective
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-07-11
    Peter Sidaway

    The findings of a single-arm cohort study involving 42 patients with refractory and/or relapsed B-cell lymphoblastic leukaemia (B-ALL) indicate that low-dose (1 × 105/kg) chimeric antigen receptor (CAR) T cells are safe and effective in this setting. 90% of patients entered complete remission,

    更新日期:2017-08-22
  • Immunotherapy: Reality check for nivolumab in advanced-stage melanoma
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-07-18
    Diana Romero

    Nivolumab, a monoclonal antibody targeting PD-1, is an immunotherapeutic agent commonly used as a systemic therapy for patients with advanced-stage melanoma. The importance of a well-planned treatment regimen to the outcomes of patients receiving this agent has been highlighted in two new studies.In the

    更新日期:2017-08-22
  • Pancreatic Cancer: EGFR inhibition is effective against KRAS-wild-type disease
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-07-25
    Peter Sidaway

    Patients diagnosed with pancreatic cancer have a poor prognosis and new therapeutic approaches are urgently required. Now, the findings of a randomized phase IIb study provide a potential new first-line treatment regimen for patients with KRAS-wild-type advanced-stage and/or metastatic pancreatic cancer.Investigators selected the

    更新日期:2017-08-22
  • Breast cancer: Profiling of ultra-low-risk disease
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-07-18
    David Killock

    Early detection of breast cancer via mammographic screening has contributed to the improvements in patient outcomes. Earlier detection, however, brings the risk of overtreatment. Molecular profiling assays have proven utility in identifying women with 'low-risk' disease who can be spared adjuvant chemotherapy. Now, new data

    更新日期:2017-08-22
  • Prostate cancer: Mutations in ctDNA reflect features of metastatic disease
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-07-18
    Peter Sidaway

    Regular biopsy sampling enables the personalized management of patients with metastatic castration-resistant prostate cancer (mCRPC); however, such sampling is invasive, carries the risk of complications, and might fail to capture all of the specific characteristics of a patient's disease. Now, a systematic comparison of matched

    更新日期:2017-08-22
  • Prevention: Low-fat diet linked to decline in breast cancer mortality
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-07-18
    Lisa Hutchinson

    Early findings from the Women's Health Initiative Dietary Modification (WHI DM) trial indicated a reduction in breast cancer mortality in women who followed a low-fat diet. Now, long-term follow-up data from this prevention trial, spanning >16 years, have been reported. As lead author, Rowan Chlebowski,

    更新日期:2017-08-22
  • Outcomes research: Integrating PROs into the clinic — overall survival benefit or not, it's worth the trouble
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-07-18
    Elisa Sperti, Massimo Di Maio

    In 2016, results of an important randomized trial demonstrated that patients undergoing chemotherapy who reported symptoms electronically have a better quality of life than those receiving usual care. Now, a significant survival improvement for patients in the experimental arm of this study has been reported. The emphasis of this survival benefit is 'culturally' positive, promoting the adoption of patient-reported outcomes in clinical practice.

    更新日期:2017-08-22
  • Haematological cancer: Staging and restaging patients with lymphoma — a better approach?
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-06-20
    Vijaya R. Bhatt, James O. Armitage

    Response criteria for disease assessment have important therapeutic and prognostic implications in clinical trials and in routine clinical practice. The Lugano classification has been used widely for evaluation of the response of patients with lymphoma to treatment, although the alternative Response Evaluation Criteria In Lymphoma 2017 (RECIL 2017) classification was recently proposed; these criteria are compared herein.

    更新日期:2017-08-22
  • Integrating liquid biopsies into the management of cancer
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-03-02
    Giulia Siravegna, Silvia Marsoni, Salvatore Siena, Alberto Bardelli

    During cancer progression and treatment, multiple subclonal populations of tumour cells compete with one another, with selective pressures leading to the emergence of predominant subclones that replicate and spread most proficiently, and are least susceptible to treatment. At present, the molecular landscapes of solid tumours are established using surgical or biopsy tissue samples. Tissue-based tumour profiles are, however, subject to sampling bias, provide only a snapshot of tumour heterogeneity, and cannot be obtained repeatedly. Genomic profiles of circulating cell-free tumour DNA (ctDNA) have been shown to closely match those of the corresponding tumours, with important implications for both molecular pathology and clinical oncology. Analyses of circulating nucleic acids, commonly referred to as 'liquid biopsies', can be used to monitor response to treatment, assess the emergence of drug resistance, and quantify minimal residual disease. In addition to blood, several other body fluids, such as urine, saliva, pleural effusions, and cerebrospinal fluid, can contain tumour-derived genetic information. The molecular profiles gathered from ctDNA can be further complemented with those obtained through analysis of circulating tumour cells (CTCs), as well as RNA, proteins, and lipids contained within vesicles, such as exosomes. In this Review, we examine how different forms of liquid biopsies can be exploited to guide patient care and should ultimately be integrated into clinical practice, focusing on liquid biopsy of ctDNA — arguably the most clinically advanced approach.

    更新日期:2017-08-22
  • Unravelling the biology of SCLC: implications for therapy
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-05-23
    Joshua K. Sabari, Benjamin H. Lok, James H. Laird, John T. Poirier, Charles M. Rudin

    Small-cell lung cancer (SCLC) is an aggressive malignancy associated with a poor prognosis. First-line treatment has remained unchanged for decades, and a paucity of effective treatment options exists for recurrent disease. Nonetheless, advances in our understanding of SCLC biology have led to the development of novel experimental therapies. Poly [ADP-ribose] polymerase (PARP) inhibitors have shown promise in preclinical models, and are under clinical investigation in combination with cytotoxic therapies and inhibitors of cell-cycle checkpoints.Preclinical data indicate that targeting of histone-lysine N-methyltransferase EZH2, a regulator of chromatin remodelling implicated in acquired therapeutic resistance, might augment and prolong chemotherapy responses. High expression of the inhibitory Notch ligand Delta-like protein 3 (DLL3) in most SCLCs has been linked to expression of Achaete-scute homologue 1 (ASCL1; also known as ASH-1), a key transcription factor driving SCLC oncogenesis; encouraging preclinical and clinical activity has been demonstrated for an anti-DLL3-antibody–drug conjugate. The immune microenvironment of SCLC seems to be distinct from that of other solid tumours, with few tumour-infiltrating lymphocytes and low levels of the immune-checkpoint protein programmed cell death 1 ligand 1 (PD-L1). Nonetheless, immunotherapy with immune-checkpoint inhibitors holds promise for patients with this disease, independent of PD-L1 status. Herein, we review the progress made in uncovering aspects of the biology of SCLC and its microenvironment that are defining new therapeutic strategies and offering renewed hope for patients.

    更新日期:2017-08-22
  • Targeting c-MET in gastrointestinal tumours: rationale, opportunities and challenges
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-04-04
    Conor A. Bradley, Manuel Salto-Tellez, Pierre Laurent-Puig, Alberto Bardelli, Christian Rolfo, Josep Tabernero, Hajrah A. Khawaja, Mark Lawler, Patrick G. Johnston, Sandra Van Schaeybroeck

    Data from many preclinical studies, including those using cellular models of colorectal, gastric, gastro-oesophageal and gastro-oesophageal junction cancers, indicate that the hepatocyte growth factor (HGF)–hepatocyte growth factor receptor (c-MET) pathway is vital for the growth, survival and invasive potential of gastrointestinal cancers. Following the availability of data from these various studies, and data on c-MET expression as a biomarker that indicates a poor prognosis in patients with gastrointestinal cancer and increased c-MET expression, inhibitors targeting this pathway have entered the clinic in the past decade. However, the design of clinical trials that incorporate the use of HGF/c-MET inhibitors in their most appropriate genetic and molecular context remains crucial. Recognizing and responding to this challenge, the European Commission funded Framework 7 MErCuRIC programme is running a biomarker-enriched clinical trial investigating the efficacy of combined c-MET/MEK inhibition in patients with RAS-mutant or RAS-wild-type metastatic colorectal cancer with aberrant c-MET expression. The design of this trial enables the continued refinement of the predictive biomarker and co-development of companion diagnostics. In this Review, we focus on advances in our understanding of inhibition of the HGF/c-MET pathway in patients with gastro-intestinal cancers, the prominent challenges facing the clinical translation and implementation of agents targeting HGF/c-MET, and discuss the various efforts, and associated obstacles to the discovery and validation of biomarkers that will enable patient stratification in this context.

    更新日期:2017-08-22
  • The changing landscape of clinical trial and approval processes in China
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-02-14
    Qing Zhou, Xiao-Yuan Chen, Zhi-Min Yang, Yi-Long Wu

    In the past decade, the standards of clinical trials in China have moved closer to international standards, thus encouraging the development of innovative drugs. However, a large backlog of pending applications for both drug approval and clinical trial registration has arisen owing to the complexity

    更新日期:2017-08-22
  • Combining drugs and extending treatment — a PFS end point is not sufficient
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-05-23
    Bishal Gyawali, Vinay Prasad

    In studies investigating the combination of two or more anticancer drugs that are already approved for independent use, or 'maintenance' regimens, the use of progression-free survival as the end point for approval is inadequate; sequential treatment with the same agents or existing salvage therapies, respectively, might provide an equivalent survival benefit, with lower toxicity, cost, and treatment burden, therefore, the use of an overall survival end point is essential to justify such interventions.

    更新日期:2017-08-22
  • Outcomes research: Integrating PROs into the clinic — overall survival benefit or not, it's worth the trouble
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-07-18
    Elisa Sperti, Massimo Di Maio

    In 2016, results of an important randomized trial demonstrated that patients undergoing chemotherapy who reported symptoms electronically have a better quality of life than those receiving usual care. Now, a significant survival improvement for patients in the experimental arm of this study has been reported. The emphasis of this survival benefit is 'culturally' positive, promoting the adoption of patient-reported outcomes in clinical practice.

    更新日期:2017-08-18
  • Haematological cancer: Staging and restaging patients with lymphoma — a better approach?
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-06-20
    Vijaya R. Bhatt, James O. Armitage

    Response criteria for disease assessment have important therapeutic and prognostic implications in clinical trials and in routine clinical practice. The Lugano classification has been used widely for evaluation of the response of patients with lymphoma to treatment, although the alternative Response Evaluation Criteria In Lymphoma 2017 (RECIL 2017) classification was recently proposed; these criteria are compared herein.

    更新日期:2017-08-18
  • Integrating liquid biopsies into the management of cancer
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-03-02
    Giulia Siravegna, Silvia Marsoni, Salvatore Siena, Alberto Bardelli

    During cancer progression and treatment, multiple subclonal populations of tumour cells compete with one another, with selective pressures leading to the emergence of predominant subclones that replicate and spread most proficiently, and are least susceptible to treatment. At present, the molecular landscapes of solid tumours are established using surgical or biopsy tissue samples. Tissue-based tumour profiles are, however, subject to sampling bias, provide only a snapshot of tumour heterogeneity, and cannot be obtained repeatedly. Genomic profiles of circulating cell-free tumour DNA (ctDNA) have been shown to closely match those of the corresponding tumours, with important implications for both molecular pathology and clinical oncology. Analyses of circulating nucleic acids, commonly referred to as 'liquid biopsies', can be used to monitor response to treatment, assess the emergence of drug resistance, and quantify minimal residual disease. In addition to blood, several other body fluids, such as urine, saliva, pleural effusions, and cerebrospinal fluid, can contain tumour-derived genetic information. The molecular profiles gathered from ctDNA can be further complemented with those obtained through analysis of circulating tumour cells (CTCs), as well as RNA, proteins, and lipids contained within vesicles, such as exosomes. In this Review, we examine how different forms of liquid biopsies can be exploited to guide patient care and should ultimately be integrated into clinical practice, focusing on liquid biopsy of ctDNA — arguably the most clinically advanced approach.

    更新日期:2017-08-18
  • Targeting c-MET in gastrointestinal tumours: rationale, opportunities and challenges
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-04-04
    Conor A. Bradley, Manuel Salto-Tellez, Pierre Laurent-Puig, Alberto Bardelli, Christian Rolfo, Josep Tabernero, Hajrah A. Khawaja, Mark Lawler, Patrick G. Johnston, Sandra Van Schaeybroeck

    Data from many preclinical studies, including those using cellular models of colorectal, gastric, gastro-oesophageal and gastro-oesophageal junction cancers, indicate that the hepatocyte growth factor (HGF)–hepatocyte growth factor receptor (c-MET) pathway is vital for the growth, survival and invasive potential of gastrointestinal cancers. Following the availability of data from these various studies, and data on c-MET expression as a biomarker that indicates a poor prognosis in patients with gastrointestinal cancer and increased c-MET expression, inhibitors targeting this pathway have entered the clinic in the past decade. However, the design of clinical trials that incorporate the use of HGF/c-MET inhibitors in their most appropriate genetic and molecular context remains crucial. Recognizing and responding to this challenge, the European Commission funded Framework 7 MErCuRIC programme is running a biomarker-enriched clinical trial investigating the efficacy of combined c-MET/MEK inhibition in patients with RAS-mutant or RAS-wild-type metastatic colorectal cancer with aberrant c-MET expression. The design of this trial enables the continued refinement of the predictive biomarker and co-development of companion diagnostics. In this Review, we focus on advances in our understanding of inhibition of the HGF/c-MET pathway in patients with gastro-intestinal cancers, the prominent challenges facing the clinical translation and implementation of agents targeting HGF/c-MET, and discuss the various efforts, and associated obstacles to the discovery and validation of biomarkers that will enable patient stratification in this context.

    更新日期:2017-08-18
  • Unravelling the biology of SCLC: implications for therapy
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-05-23
    Joshua K. Sabari, Benjamin H. Lok, James H. Laird, John T. Poirier, Charles M. Rudin

    Small-cell lung cancer (SCLC) is an aggressive malignancy associated with a poor prognosis. First-line treatment has remained unchanged for decades, and a paucity of effective treatment options exists for recurrent disease. Nonetheless, advances in our understanding of SCLC biology have led to the development of novel experimental therapies. Poly [ADP-ribose] polymerase (PARP) inhibitors have shown promise in preclinical models, and are under clinical investigation in combination with cytotoxic therapies and inhibitors of cell-cycle checkpoints.Preclinical data indicate that targeting of histone-lysine N-methyltransferase EZH2, a regulator of chromatin remodelling implicated in acquired therapeutic resistance, might augment and prolong chemotherapy responses. High expression of the inhibitory Notch ligand Delta-like protein 3 (DLL3) in most SCLCs has been linked to expression of Achaete-scute homologue 1 (ASCL1; also known as ASH-1), a key transcription factor driving SCLC oncogenesis; encouraging preclinical and clinical activity has been demonstrated for an anti-DLL3-antibody–drug conjugate. The immune microenvironment of SCLC seems to be distinct from that of other solid tumours, with few tumour-infiltrating lymphocytes and low levels of the immune-checkpoint protein programmed cell death 1 ligand 1 (PD-L1). Nonetheless, immunotherapy with immune-checkpoint inhibitors holds promise for patients with this disease, independent of PD-L1 status. Herein, we review the progress made in uncovering aspects of the biology of SCLC and its microenvironment that are defining new therapeutic strategies and offering renewed hope for patients.

    更新日期:2017-08-18
  • The changing landscape of clinical trial and approval processes in China
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-02-14
    Qing Zhou, Xiao-Yuan Chen, Zhi-Min Yang, Yi-Long Wu

    The expansion of research and development of anticancer drugs in China has resulted in considerable delays in the approval of both clinical trials of novel agents, and the marketing approval of these agents once tested. In this Perspective, the authors describe the measures taken by the Chinese FDA to address these challenges in a rapidly developing research environment.

    更新日期:2017-08-18
  • Combining drugs and extending treatment — a PFS end point is not sufficient
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-05-23
    Bishal Gyawali, Vinay Prasad

    In studies investigating the combination of two or more anticancer drugs that are already approved for independent use, or 'maintenance' regimens, the use of progression-free survival as the end point for approval is inadequate; sequential treatment with the same agents or existing salvage therapies, respectively, might provide an equivalent survival benefit, with lower toxicity, cost, and treatment burden, therefore, the use of an overall survival end point is essential to justify such interventions.

    更新日期:2017-08-18
  • WIN to avoid the valley of death
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-07-20

    The extraordinary scientific and technical advances in basic and translational cancer research, coupled with our increased knowledge of the nonmalignant and cancer genomes has changed our understanding of the multitude of diseases termed cancer, at every level: these advances include diagnosis, screening, prognosis, treatment, clinical

    更新日期:2017-08-18
  • Targeted therapies: Defining the best-in-class in NSCLC
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-06-27
    Lisa Hutchinson

    For patients with ALK-positive non-small-cell lung cancer (NSCLC) the standard first-line therapy is crizotinib. Resistance to first-line ALK inhibitors is common — inevitably, patients relapse, and can develop metastases in the central nervous system (CNS). The second-generation ALK inhibitor alectinib is able to penetrate the

    更新日期:2017-08-18
  • Targeted therapies: Lenvatinib SELECTs survival benefit
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-07-11
    Lisa Hutchinson

    Until the past 4 years, no treatment option existed for patients with refractory differentiated thyroid cancer, who were treated routinely with supportive care. The first drug to be approved for these patients by the FDA was sorafenib in 2013, followed by lenvatinib in 2015 —

    更新日期:2017-08-18
  • Lung Cancer: Frontline nivolumab — CheckMate 026 ends in stalemate
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-07-20
    David Killock

    The anti-PD-1 antibody nivolumab is an approved second-line therapy for advanced-stage non-small-cell lung cancer (NSCLC), but earlier use of this immunotherapeutic agent might be beneficial. In the phase III CheckMate 026 trial, David Carbone et al. addressed this question.The researchers randomly assigned

    更新日期:2017-08-18
  • Haematological cancer: Genomic disruption of CD7 avoids fractricide
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-06-13
    Peter Sidaway

    The risk of T-cell fractricide, a situation in which chimeric antigen receptor (CAR) T cells are toxic to each other, owing to the expression of multiple shared antigens by malignant and nonmalignant cells, precludes the use of CAR T-cell-based therapies in patients with T-cell malignancies.

    更新日期:2017-08-18
  • Immunotherapy: Neuropilin-1 is required for Treg stability
    Nat. Rev. Clin. Oncol. (IF 20.693) Pub Date : 2017-06-13
    Peter Sidaway

    The development of an anticancer immune response is often precluded by an immunosuppressive microenvironment, which can be created by the presence of large numbers of regulatory T cells (Treg). The findings of research using a mouse model of melanoma demonstrate the importance of

    更新日期:2017-08-18
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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