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  • MGMT Status as a Clinical Biomarker in Glioblastoma
    Trends Cancer (IF 8.884) Pub Date : 2020-03-27
    Madison Butler; Lorinc Pongor; Yu-Ting Su; Liqiang Xi; Mark Raffeld; Martha Quezado; Jane Trepel; Kenneth Aldape; Yves Pommier; Jing Wu

    Glioblastoma is the most common primary malignant brain tumor. Although current standard therapy extends median survival to ~15 months, most patients do not have a sustained response to treatment. While O6-methylguanine (O6-MeG)-DNA methyltransferase (MGMT) promoter methylation status is accepted as a prognostic and promising predictive biomarker in glioblastoma, its value in informing treatment decisions

  • Drilling for Oil: Tumor-Surrounding Adipocytes Fueling Cancer
    Trends Cancer (IF 8.884) Pub Date : 2020-03-26
    Camille Attané; Catherine Muller

    Over the past decade, it has become apparent that metabolic reprogramming is a key event in tumor progression. The tumor microenvironment (TME) is a source of metabolites for tumor cells. Lipid-filled mature adipocytes are frequently found in proximity to invasive human tumors and release free fatty acids (FFAs) through lipolysis. These FFAs are taken up by tumor cells and used to promote tumor progression

  • Tumour Cell Secretome in Chemoresistance and Tumour Recurrence
    Trends Cancer (IF 8.884) Pub Date : 2020-03-25
    Emma C. Madden; Adrienne M. Gorman; Susan E. Logue; Afshin Samali

    Chemoresistance is a major factor driving tumour relapse and the high rates of cancer-related deaths. Understanding how cancer cells overcome chemotherapy-induced cell death is critical in promoting patient survival. One emerging mechanism of chemoresistance is the tumour cell secretome (TCS), an array of protumorigenic factors released by tumour cells. Chemotherapy exposure can also alter the composition

  • Mechanisms Underlying Recurrent Genomic Amplification in Human Cancers
    Trends Cancer (IF 8.884) Pub Date : 2020-03-24
    Hisashi Tanaka; Takaaki Watanabe

    Focal copy-number increases (genomic amplification) pinpoint oncogenic driver genes and therapeutic targets in cancer genomes. With the advent of genomic technologies, recurrent genomic amplification has been mapped throughout the genome. Recurrent amplification could be solely due to positive selection for the tumor-promoting effects of amplified gene products. Alternatively, recurrence could result

  • Turning Cold into Hot: Firing up the Tumor Microenvironment
    Trends Cancer (IF 8.884) Pub Date : 2020-03-21
    Qianqian Duan; Hualing Zhang; Junnian Zheng; Lianjun Zhang

    Cancers develop within complex tissue environments consisting of diverse innate and adaptive immune cells, along with stromal cells, vascular networks, and many other cellular and noncellular components. The high heterogeneity within the tumor microenvironment (TME) remains a key obstacle in understanding and treating cancer. Understanding the dynamic functional interplay within this intricate ecosystem

  • RAC1 as a Therapeutic Target in Malignant Melanoma
    Trends Cancer (IF 8.884) Pub Date : 2020-03-18
    Alexa C. Cannon; Cristina Uribe-Alvarez; Jonathan Chernoff

    Small GTPases of the RAS and RHO families are related signaling proteins that, when activated by growth factors or by mutation, drive oncogenic processes. While activating mutations in KRAS, NRAS, and HRAS genes have long been recognized and occur in many types of cancer, similar mutations in RHO family genes, such as RAC1 and RHOA, have only recently been detected as the result of extensive cancer

  • Immune Cell-Derived Exosomes in the Cancer-Immunity Cycle
    Trends Cancer (IF 8.884) Pub Date : 2020-03-17
    Wei Yan; Shuai Jiang

    Cells can communicate through extracellular vesicle (EV) secretion and uptake. Exosomes are lipid bilayer-enclosed EVs of 30–150 nm in diameter, which can transfer RNA, functional proteins, lipids, and metabolites to recipient cells in vivo. Most cell types, including immune cells, can secrete and uptake exosomes. Biogenesis, secretion, and uptake of immune cell-derived exosomes are regulated by intracellular

  • Lipid in Renal Carcinoma: Queen Bee to Target?
    Trends Cancer (IF 8.884) Pub Date : 2020-03-17
    Sze Kiat Tan; Scott M. Welford

    Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer subtype, characterized by a lipid storage phenotype. We found that carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme of mitochondrial fatty acid (FA) transport, is repressed by hypoxia-inducible factors (HIFs), reducing FA oxidation (FAO). Altering lipid metabolism may be a new therapeutic avenue in ccRCC.

  • Translin-Trax: Considerations for Oncological Therapeutic Targeting
    Trends Cancer (IF 8.884) Pub Date : 2020-03-16
    Ramsay J. McFarlane; Jane A. Wakeman

    Dicer-deficient cancers have poor prognoses, which is linked to the degradation of tumour-suppressing miRNA precursors by the Translin-Trax (Tn-Tx) ribonuclease. Inhibition of Tn-Tx potentially offers a new therapeutic intervention point. However, Tn-Tx functions in an array of biological processes, and here we consider how this complexity could influence therapeutic design strategies.

  • Pediatric Cancer Models in Zebrafish
    Trends Cancer (IF 8.884) Pub Date : 2020-03-13
    Mattie J. Casey; Rodney A. Stewart

    Pediatric cancer is a leading cause of death in children and adolescents. Improvements in pediatric cancer treatment that include the alleviation of long-term adverse effects require a deeper understanding of the genetic, epigenetic, and developmental factors driving these cancers. Here, we review how the unique attributes of the zebrafish model system in embryology, imaging, and scalability have been

  • Perturbation-Driven Entropy as a Source of Cancer Cell Heterogeneity
    Trends Cancer (IF 8.884) Pub Date : 2020-03-13
    Sebastian M.B. Nijman

    Intratumor heterogeneity is a key hallmark of cancer that contributes to progression and therapeutic resistance. Phenotypic heterogeneity is in part caused by Darwinian selection of subclones that arise by random (epi)genetic aberrations. In addition, cancer cells are endowed with increased cellular plasticity compared with their normal counterparts, further adding to their heterogeneous behavior.

  • PD1 Blockade in Cancer: Impact on Myeloid Cells
    Trends Cancer (IF 8.884) Pub Date : 2020-03-13
    Mai Fujiwara; Lucien P. Garo; Gopal Murugaiyan

    Programmed death 1 (PD1) has emerged as a major inhibitor of antitumor T cells, and anti-PD1 therapies have demonstrated clinical efficacy in multiple cancers. However, the impact of PD1 on other immune cells had remained unclear. A recent study by Strauss et al. describes how myeloid cell-intrinsic PD1 signaling limits myelopoiesis in cancer pertinent to anti-PD1 therapies.

  • On a New Proposed Mechanism of 5-Fluorouracil-Mediated Cytotoxicity
    Trends Cancer (IF 8.884) Pub Date : 2020-03-13
    Shobbir Hussain

    The major molecular mode of action of the cytotoxic drug 5-fluorouracil (5-FU) is generally considered to result from thymidylate synthase inhibition. Recent findings relating to the function of the human uracil-5 methyltransferase (U5MT), TRMT2A, and its interaction with 5-FU metabolites incorporated within tRNAs, lead to an additional hypothesis that is proposed here.

  • Treating the Disease, Not the Symptom: Beyond NSAIDs
    Trends Cancer (IF 8.884) Pub Date : 2020-03-12
    Robert R. Bowers; Joe R. Delaney; Demetri D. Spyropoulos

    Mitigating inflammation is clearly important in cancer prevention and control. Traditionally, pharmaceuticals have taken the lead in this problem. In an attempt to ‘head them off at the pass’, this Forum takes a hard look at the concept of ‘better living through chemicals’ and limiting proinflammatory chemicals entering the body.

  • Redox Debt Leads to Metabolic Bankruptcy in Tumors
    Trends Cancer (IF 8.884) Pub Date : 2020-03-06
    Evan Quon; Madeleine L. Hart; Lucas B. Sullivan

    Lactate dehydrogenase (LDH) accounts for the fermentative component of aerobic glycolysis, a near ubiquitous metabolic alteration in cancer. Recently, Oshima et al. developed a bioavailable LDH inhibitor that decreases tumor growth in mice and functions synergistically with mitochondrial respiration inhibitors. These findings suggest a cooperative mechanism of action that targets redox homeostasis

  • Towards the Microbial Production of Plant-Derived Anticancer Drugs
    Trends Cancer (IF 8.884) Pub Date : 2020-03-05
    Vincent Courdavault; Sarah E. O’Connor; Audrey Oudin; Sébastien Besseau; Nicolas Papon

    Many of the plant-derived compounds used in chemotherapies are currently produced by semisynthesis, which results in limited supplies at exorbitant market prices. However, the synthetic biology era, which began ca 15 years ago, has progressively yielded encouraging advances by using engineered microbes for the practical production of cheaper plant anticancer drugs.

  • Promoter DNA Hypermethylation and Paradoxical Gene Activation
    Trends Cancer (IF 8.884) Pub Date : 2020-03-04
    Jim Smith; Swapnoleena Sen; Robert J. Weeks; Michael R. Eccles; Aniruddha Chatterjee

    DNA methylation is a stable epigenetic modification that contributes to the spatiotemporal regulation of gene expression. The manner in which DNA methylation contributes to transcriptional control is dependent on the biological context, including physiological state and the properties of the DNA itself. Classically, dense promoter DNA methylation is associated with transcriptional repression. However

  • Tumor Plasticity and Resistance to Immunotherapy
    Trends Cancer (IF 8.884) Pub Date : 2020-03-04
    Lucas A. Horn; Kristen Fousek; Claudia Palena

    Tumor cell plasticity exhibited as an epithelial–mesenchymal transition (EMT) has been identified as a major obstacle for the effective treatment of many cancers. This process, which involves the dedifferentiation of epithelial tumor cells towards a motile, metastatic, and mesenchymal tumor phenotype, mediates resistance to conventional therapies and small-molecule targeted therapies. In this review

  • The Mystery of Rap1 Suppression of Oncogenic Ras
    Trends Cancer (IF 8.884) Pub Date : 2020-03-02
    Ruth Nussinov; Hyunbum Jang; Mingzhen Zhang; Chung-Jung Tsai; Anna A. Sablina

    Decades ago, Rap1, a small GTPase very similar to Ras, was observed to suppress oncogenic Ras phenotype, reverting its transformation. The proposed reason, persisting since, has been competition between Ras and Rap1 for a common target. Yet, none was found. There was also Rap1’s puzzling suppression of Raf-1 versus activation of BRAF. Reemerging interest in Rap1 envisages capturing its Ras suppression

  • Cancer Immunotherapy with CDK7 Inhibitors
    Trends Cancer (IF 8.884) Pub Date : 2020-02-28
    Giulia Petroni; Lorenzo Galluzzi

    Recent findings demonstrate that pharmacological cyclin-dependent kinase 7 (CDK7) inhibitors can evoke anticancer immunity upon genomic destabilization of neoplastic cells. Besides adding CDK7 to the expanding list of cell cycle proteins that impinge on immune regulation, these results support the value of aggravating genomic instability in cancer cells to enable immunological disease control.

  • Dark Side of Cytotoxic Therapy: Chemoradiation-Induced Cell Death and Tumor Repopulation
    Trends Cancer (IF 8.884) Pub Date : 2020-02-26
    Ming-jie Jiang; Dian-na Gu; Juan-juan Dai; Qian Huang; Ling Tian

    Accelerated tumor repopulation following chemoradiation is often observed in the clinic, but the underlying mechanisms remain unclear. In recent years, dying cells caused by chemoradiation have attracted much attention, and they may manifest diverse forms of cell death and release complex factors and thus orchestrate tumor repopulation cascades. Dying cells potentiate the survival of residual living

  • Organizing ‘Elements’: Facilitating Exocytosis and Promoting Metastasis
    Trends Cancer (IF 8.884) Pub Date : 2020-02-24
    Dominique C. Stephens; Dinari A. Harris

    For metastasis to occur, cancer cells must exocytose proteases, like matrix metalloproteinases (MMPs), that are key in extracellular matrix (ECM) degradation. Growing evidence suggests that cancer cells use distinct spatial and temporal clustering patterns or organizing ‘elements’ that facilitate secretory vesicle fusion and the subsequent exocytosis of proteins that contribute to metastasis.

  • Identification of Antigenic Targets
    Trends Cancer (IF 8.884) Pub Date : 2020-02-20
    Hans-Peter Gerber; Leah V. Sibener; Luke J. Lee; Marvin H. Gee

    The ideal cancer target antigen (Ag) is expressed at high copy numbers on neoplastic cells, absent on normal tissues, and contributes to the survival of cancer cells. Despite significant investments in the identification of cell surface Ags, there is a paucity of targets that meet such ideal cancer target criteria. Recent clinical trials in patients with cancer treated with immune checkpoint inhibitors

  • Mutagenesis by Microbe: the Role of the Microbiota in Shaping the Cancer Genome
    Trends Cancer (IF 8.884) Pub Date : 2020-02-20
    Maurice Barrett; Collette K. Hand; Fergus Shanahan; Thomas Murphy; Paul W. O’Toole

    Cancers arise through the process of somatic evolution fueled by the inception of somatic mutations. We lack a complete understanding of the sources of these somatic mutations. Humans host a vast repertoire of microbes collectively known as the microbiota. The microbiota plays a role in altering the tumor microenvironment and proliferation. In addition, microbes have been shown to elicit DNA damage

  • Gap Junctions and Breast Cancer Dormancy
    Trends Cancer (IF 8.884) Pub Date : 2020-02-20
    Garima Sinha; Alejandra I. Ferrer; Caitlyn A. Moore; Yahaira Naaldijk; Pranela Rameshwar

    Breast cancer (BC) relapse, despite clinical advancement, remains one of the biggest issues in the field. Intercellular communication, specifically via connexin (Cx)-mediated gap junctions (GJs), play a key role in the long-term survival of these, treatment-resistant breast cancer stem cells (CSCs), allowing for relapse. Both basic and clinical evidence reveal dual roles for GJs, in tumor suppression

  • Circular RNAs in Cancer: Biogenesis, Function, and Clinical Significance
    Trends Cancer (IF 8.884) Pub Date : 2020-02-19
    Jiao Li; Dan Sun; Wenchen Pu; Jin Wang; Yong Peng

    Circular RNA (circRNA) is a class of single-stranded molecules with tissue/development-specific expression patterns. Unlike linear RNA, circRNA forms a covalently closed loop produced from ‘back-splicing’ of primary transcripts, conferring on them inherent resistance to exonucleolytic RNA decay. Increasing evidence demonstrates that many circRNAs exert important biological functions by acting as miRNA

  • Brachyury: Strategies for Drugging an Intractable Cancer Therapeutic Target
    Trends Cancer (IF 8.884) Pub Date : 2020-02-19
    Helena Robinson; Ramsay J. McFarlane; Jane A. Wakeman

    New approaches to drug discovery are unlocking enormous therapeutic potential residing in cancer-specific molecules. Brachyury is emerging as an exciting new drug target for the rare bone cancer chordoma. Here, recent advances targeting Brachyury in chordoma are discussed and how these might open doors to the targeting of other, more common cancer types.

  • DNA-PK, Nuclear mTOR, and the Androgen Pathway in Prostate Cancer
    Trends Cancer (IF 8.884) Pub Date : 2020-02-18
    Vincent Giguère

    Androgen and its receptor (AR) are major drivers of prostate cancer (PCa), a leading cause of mortality in aging men. Thus, understanding the numerous mechanisms by which AR can promote the growth and proliferation of PCa cells and enable their escape from hormone-dependent therapies, eventually leading to metastasis and death of the patient, is essential to discover alternative therapeutic approaches

  • Understanding the Cause and Consequence of Tumor Heterogeneity
    Trends Cancer (IF 8.884) Pub Date : 2020-02-13
    Subreen Khatib; Yotsawat Pomyen; Hien Dang; Xin Wei Wang

    Tumor heterogeneity is a large conundrum in cancer medicine, making most therapeutic interventions palliative rather than curative. Here we discuss the implications of how molecularly targeted therapies in solid malignancies that promote limited cancer cell death may in fact make tumors more heterogeneous, increase aggressive phenotypes, and thus worsen patient outcomes.

  • PALB2 Genetic Variants: Can Functional Assays Assist Translation?
    Trends Cancer (IF 8.884) Pub Date : 2020-02-13
    Melissa C. Southey; Amanda Rewse; Tu Nguyen-Dumont

    PALB2 loss-of-function variants are associated with increased risk of breast and other cancers, but the clinical relevance of missense variants (MVs) remains uncertain. Recent findings reported by Wiltshire et al., Rodrigue et al., and Boonen et al. demonstrate that some MVs disrupt PALB2 function. This new information will support the clinical management of families who carry these MVs and inform

  • Nanotherapeutics for Immuno-Oncology: A Crossroad for New Paradigms
    Trends Cancer (IF 8.884) Pub Date : 2020-02-13
    Wantong Song; Manisit Das; Xuesi Chen

    With the rapid increase in the use of nanotechnology and immunotherapy for cancer management in the recent past, there are great implications for using nanotechnology in immuno-oncology. However, to deliver clinical success, the scientific and clinical rationale must be critically evaluated when applying nanotechnology to immuno-oncology challenges. This opinion article distinguishes between designing

  • The Cancer Microbiome: Distinguishing Direct and Indirect Effects Requires a Systemic View.
    Trends Cancer (IF 8.884) Pub Date : 2020-02-07
    Joao B Xavier,Vincent B Young,Joseph Skufca,Fiona Ginty,Traci Testerman,Alexander T Pearson,Paul Macklin,Amir Mitchell,Ilya Shmulevich,Lei Xie,J Gregory Caporaso,Keith A Crandall,Nicole L Simone,Filipa Godoy-Vitorino,Timothy J Griffin,Katrine L Whiteson,Heather H Gustafson,Daniel J Slade,Thomas M Schmidt,Marina R S Walther-Antonio,Tal Korem,Bobbie-Jo M Webb-Robertson,Mark P Styczynski,W Evan Johnson

    The collection of microbes that live in and on the human body - the human microbiome - can impact on cancer initiation, progression, and response to therapy, including cancer immunotherapy. The mechanisms by which microbiomes impact on cancers can yield new diagnostics and treatments, but much remains unknown. The interactions between microbes, diet, host factors, drugs, and cell-cell interactions

  • On Epigenetic Plasticity and Genome Topology.
    Trends Cancer (IF 8.884) Pub Date : 2020-02-07
    Charalampos Lazaris,Iannis Aifantis,Aristotelis Tsirigos

    Mounting evidence links genetic lesions with genome topology alterations and aberrant gene activation. However, the role of epigenetic plasticity remains elusive. Emerging studies implicate DNA methylation, transcriptional elongation, long noncoding RNAs (lncRNAs), and CCCTC-binding factor (CTCF)-RNA interactions, but systematic approaches are needed to fully decipher the role of epigenetic plasticity

  • Hyperprogression and Immunotherapy: Fact, Fiction, or Alternative Fact?
    Trends Cancer (IF 8.884) Pub Date : 2020-02-06
    Jacob J Adashek,Ishwaria M Subbiah,Ignacio Matos,Elena Garralda,Arjun K Menta,Dhakshina Moorthy Ganeshan,Vivek Subbiah

    Immunotherapy (IO) has altered the therapeutic landscape for multiple cancers. There are emerging data from retrospective studies on a subset of patients who do not benefit from IO, instead experiencing rapid progression with dramatic acceleration of disease trajectory, termed 'hyperprogressive disease' (HPD). The incidence of HPD ranges from 4% to 29% from the studies reported. Biological basis and

  • Immune Checkpoint Inhibition in Prostate Cancer.
    Trends Cancer (IF 8.884) Pub Date : 2020-02-06
    Lowell Thorndike Nicholson,Lawrence Fong

    Although immunotherapy has proved to be effective in a variety of cancer subtypes, the role of immune checkpoint inhibition in the treatment of prostate cancer remains unclear. Here we review results from the latest clinical trials and discuss data suggesting that certain genetic mutations may confer increased sensitivity to immune checkpoint blockade.

  • Organoids: A Platform Ready for Glioblastoma Precision Medicine?
    Trends Cancer (IF 8.884) Pub Date : 2020-02-06
    Wei-Lin Jin; Ming-Zhu Jin; Yan-Yang Tu

    Patient-derived organoids can recapitulate parental tumor heterogeneity. In a recent study in Cell, Jacob et al. cultivated glioblastoma organoids (GBOs) to mimic tumor heterogeneity and chimeric antigen receptor (CAR)-T cell immunotherapy, applied it for xenograft establishment and drug testing, and generated a biobank for the timely start of post-operation therapy.

  • TP53 Mutations and Outcomes in Breast Cancer: Reading beyond the Headlines.
    Trends Cancer (IF 8.884) Pub Date : 2020-02-05
    Ashkan Shahbandi,Hoang D Nguyen,James G Jackson

    TP53 is the most frequently mutated gene in breast cancer, but its role in survival is confounded by different studies concluding that TP53 mutations are associated with negative, neutral, or positive outcomes. Closer examination showed that many studies were limited by factors such as imprecise methods to detect TP53 mutations and small cohorts that combined patients treated with drugs having very

  • Optical Microscopy and Coherence Tomography of Cancer in Living Subjects.
    Trends Cancer (IF 8.884) Pub Date : 2020-02-05
    Peng Si,Alexander Honkala,Adam de la Zerda,Bryan Ronain Smith

    Intravital microscopy (IVM) and optical coherency tomography (OCT) are two powerful optical imaging tools that allow visualization of dynamic biological activities in living subjects with subcellular resolutions. Recent advances in labeling and label-free techniques empower IVM and OCT for a wide range of preclinical and clinical cancer imaging, providing profound insights into the complex physiological

  • Glioblastoma Stem Cells: Driving Resilience through Chaos.
    Trends Cancer (IF 8.884) Pub Date : 2020-02-03
    Briana C Prager,Shruti Bhargava,Vaidehi Mahadev,Christopher G Hubert,Jeremy N Rich

    Glioblastoma is an aggressive and heterogeneous tumor in which glioblastoma stem cells (GSCs) are at the apex of an entropic hierarchy and impart devastating therapy resistance. The high entropy of GSCs is driven by a permissive epigenetic landscape and a mutational landscape that revokes crucial cellular checkpoints. The GSC population encompasses a complex array of diverse microstates that are defined

  • Diagnostic Power of DNA Methylation Classifiers for Early Detection of Cancer.
    Trends Cancer (IF 8.884) Pub Date : 2020-02-03
    Dhruvajyoti Roy,Maarit Tiirikainen

    DNA methylation-based epigenetic signatures have become valuable cancer biomarkers. We highlight the advantages of liquid biopsy based DNA-methylation profiling for noninvasive diagnosis of early stage cancers and discuss the advanced analytical approaches developed by commercial and academic partnerships.

  • Premortem Tumor Stress in Radioimmunotherapy.
    Trends Cancer (IF 8.884) Pub Date : 2020-01-27
    Ignacio Melero,Maite Alvarez,Luna Minute,Pedro Berraondo

    Recent investigations (Rodriguez-Ruiz et al.) have established the counterintuitive idea that delaying apoptosis upon tumor irradiation by caspase 3 inhibition in tumor cells raises the immunogenicity of dying malignant cells.

  • Alternative Lengthening of Telomeres: Building Bridges To Connect Chromosome Ends.
    Trends Cancer (IF 8.884) Pub Date : 2020-01-23
    Song My Hoang,Roderick J O'Sullivan

    Alternative lengthening of telomeres (ALT) is a mechanism of telomere maintenance that is observed in many of the most recalcitrant cancer subtypes. Telomeres in ALT cancer cells exhibit a distinctive nucleoprotein architecture shaped by the mismanagement of chromatin that fosters cycles of DNA damage and replicative stress that activate homology-directed repair (HDR). Mutations in specific chromatin-remodeling

  • Colorectal Cancer Modeling with Organoids: Discriminating between Oncogenic RAS and BRAF Variants.
    Trends Cancer (IF 8.884) Pub Date : 2020-01-21
    Jasmin B Post,Jeanine M L Roodhart,Hugo J G Snippert

    RAS and BRAF proteins are frequently mutated in colorectal cancer (CRC) and have been associated with therapy resistance in metastatic CRC patients. RAS isoforms are considered to act as redundant entities in physiological and pathological settings. However, there is compelling evidence that mutant variants of RAS and BRAF have different oncogenic potentials and therapeutic outcomes. In this review

  • Trastuzumab Emtansine: Mechanisms of Action and Resistance, Clinical Progress, and Beyond.
    Trends Cancer (IF 8.884) Pub Date : 2020-01-21
    Sara García-Alonso,Alberto Ocaña,Atanasio Pandiella

    The approval of ado-trastuzumab emtansine (T-DM1) for clinical use represented a turning point both in HER2-positive breast cancer treatment and antibody-drug conjugate (ADC) technology. T-DM1 has proved its value and effectiveness in advanced metastatic disease as well as in the adjuvant setting. However, its therapeutic potential extends beyond the treatment of breast cancer. Around 100 clinical

  • The Influence of Lung Microbiota on Lung Carcinogenesis, Immunity, and Immunotherapy.
    Trends Cancer (IF 8.884) Pub Date : 2020-01-18
    Ariel G Ramírez-Labrada,Dolores Isla,Angel Artal,Maykel Arias,Antonio Rezusta,Julián Pardo,Eva M Gálvez

    Microbiota have emerged as key modulators of both the carcinogenic process and the immune response against cancer cells, and, thus, it seems to influence the efficacy of immunotherapy. While most studies have focused on analyzing the influence of gut microbiota, its composition substantially differs from that in the lung. Here, we describe how microbial life in the lungs is associated with host immune

  • Targeting the Tumor Microenvironment in Colorectal Peritoneal Metastases.
    Trends Cancer (IF 8.884) Pub Date : 2020-01-16
    Wim Ceelen,Robert G Ramsay,Vignesh Narasimhan,Alexander G Heriot,Olivier De Wever

    Peritoneal metastasis (PM) occurs in approximately one in four colorectal cancer (CRC) patients. The pathophysiology of colorectal PM remains poorly characterized. Also, the efficacy of current treatment modalities, including surgery and intraperitoneal (IP) delivery of chemotherapy, is limited. Increasingly, therefore, efforts are being developed to unravel the PM cascade and at understanding the

  • Targeting the Unfolded Protein Response in Hormone-Regulated Cancers.
    Trends Cancer (IF 8.884) Pub Date : 2020-01-16
    Yang Jin,Fahri Saatcioglu

    Cancer cells exploit many of the cellular adaptive responses to support their survival needs. One of these is the unfolded protein response (UPR), a highly conserved signaling pathway that is mounted in response to endoplasmic reticulum (ER) stress. Recent work showed that steroid hormones, in particular estrogens and androgens, regulate the canonical UPR pathways in breast cancer (BCa) and prostate

  • Mechanistic Links between Obesity, Insulin, and Cancer.
    Trends Cancer (IF 8.884) Pub Date : 2020-01-14
    Rachel J Perry,Gerald I Shulman

    Obesity and type 2 diabetes (T2D) increase the prevalence and worsen the prognosis of more than a dozen tumor types; however, the mechanism for this association remains hotly debated. Here we discuss a potential role for insulin as the key hormonal mediator of tumor metabolism and growth in obesity-associated insulin resistance.

  • Therapeutic Application of PARP Inhibitors in Neuro-Oncology.
    Trends Cancer (IF 8.884) Pub Date : 2020-01-13
    Jianfang Ning,Hiroaki Wakimoto

    In response to a variety of cellular stresses, poly(ADP-ribose) polymerase 1 (PARP1) has vital roles in orchestrating DNA damage repair and preserving genomic integrity. Clinical activity of PARP inhibitors (PARPis) in BRCA1/2 mutant cancers validated the concept of synthetic lethality between PARP inhibition and deleterious BRCA1/2 mutations, leading to clinical approval of several PARPis. Preclinical

  • Agrin Mediates Angiogenesis in the Tumor Microenvironment.
    Trends Cancer (IF 8.884) Pub Date : 2020-01-09
    Sayan Chakraborty,Kizito Njah,Wanjin Hong

    Angiogenesis represents a hallmark of cancer. Several proteoglycans associate with cell surface receptors and regulate angiogenesis within the tumor microenvironment (TME). We highlight the recent discovery that the proteoglycan Agrin cross talks between the tumor and the endothelium to promote an angiogenesis privileged niche during cancer progression.

  • Tumor Functional Heterogeneity Unraveled by scRNA-seq Technologies.
    Trends Cancer (IF 8.884) Pub Date : 2020-01-03
    Laura González-Silva,Laura Quevedo,Ignacio Varela

    Effective cancer treatment has been precluded by the presence of various forms of intratumoral complexity that drive treatment resistance and metastasis. Recent single-cell sequencing technologies are significantly facilitating the characterization of tumor internal architecture during disease progression. New applications and advances occurring at a fast pace predict an imminent broad application

  • Metabolic Fitness and Plasticity in Cancer Progression.
    Trends Cancer (IF 8.884) Pub Date : 2020-01-03
    Shawn McGuirk,Yannick Audet-Delage,Julie St-Pierre

    Cancer cells have enhanced metabolic needs due to their rapid proliferation. Moreover, throughout their progression from tumor precursors to metastases, cancer cells face challenging physiological conditions, including hypoxia, low nutrient availability, and exposure to therapeutic drugs. The ability of cancer cells to tailor their metabolic activities to support their energy demand and biosynthetic

  • Targeting NAD+ Synthesis to Potentiate CD38-Based Immunotherapy of Multiple Myeloma.
    Trends Cancer (IF 8.884) Pub Date : 2019-12-31
    Barry E Kennedy,Maryanne Sadek,Manal O Elnenaei,Anthony Reiman,Shashi A Gujar

    Antibodies targeting CD38, a NAD+-degrading enzyme, have emerged as a promising immunotherapy against multiple myeloma (MM). Currently, the mechanisms by which anti-CD38 antibodies establish their therapeutic effects are poorly understood. Here, we advocate for the depletion of NAD+ to enhance the efficacy of anti-CD38-based immunotherapies in MM.

  • Immunotherapeutic Transport Oncophysics: Space, Time, and Immune Activation in Cancer.
    Trends Cancer (IF 8.884) Pub Date : 2019-12-30
    Sara Nizzero,Haifa Shen,Mauro Ferrari,Bruna Corradetti

    Immuno-oncology has gained momentum thanks to the success of strategies aimed at enhancing immune-mediated antitumor response. The field of immunotherapeutic transport oncophysics investigates the physical processes that drive cancer immunotherapies. This review discusses three main aspects that determine the outcome of an immunotherapy-based treatment from a physical point of view; (i) space, the

  • Mutant p53 on the Path to Metastasis.
    Trends Cancer (IF 8.884) Pub Date : 2019-12-16
    Qiaosi Tang,Zhenyi Su,Wei Gu,Anil K Rustgi

    Metastasis contributes to the vast majority of cancer-related mortality. Regulatory mechanisms of the multistep invasion-metastasis cascade are being unraveled. TP53 is the most frequently mutated gene across human cancers. Accumulating evidence has shown that mutations of TP53 not only lead to loss of function or dominant negative effects, but also promotes a gain of function. Specifically, gain of

  • Decoding the Biology of Exosomes in Metastasis.
    Trends Cancer (IF 8.884) Pub Date : 2019-12-10
    Bárbara Adem,Patricia F Vieira,Sonia A Melo

    Metastasis is the leading cause of cancer mortality. Cancer cells must adapt to colonize and thrive at the metastatic site. The modulation of the receptive organ microenvironment is a key event in the adaptation process and is partially accomplished at a distance by the primary tumor. Exosomes, a subclass of extracellular vesicles (EVs), are distal mediators of communication that carry genetic and

  • Evolving Significance of Tumor-Normal Sequencing in Cancer Care.
    Trends Cancer (IF 8.884) Pub Date : 2019-12-10
    Diana Mandelker,Ozge Ceyhan-Birsoy

    Molecular tests assist at various stages of cancer patient management, including providing diagnosis, predicting prognosis, identifying therapeutic targets, and determining hereditary cancer risk. The current testing paradigm involves germline testing in a subset of patients determined to be at high risk for having a hereditary cancer syndrome, and tumor-only sequencing for treatment decisions in advanced

  • Does Neuronal Activity Promote Glioma Progression?
    Trends Cancer (IF 8.884) Pub Date : 2019-12-07
    Hans-Georg Wirsching,Michael Weller

    Excessive glutamate release by glioma cells induces pharmacologically accessible neuronal hyperexcitation, including epilepsy. Two recent reports by Venkataramani et al. and Venkatesh et al. suggest that neuronal hyperexcitation stimulates bona fide glutamatergic synapses on glioma cells. Ionotropic glutamate receptors activate intercellular calcium signaling networks to orchestrate glioma cell growth

  • Peripheral Circulating CD45RA-FOXP3hi T Regulatory (TReg) II Cells Provide a Window into the Activity of Intratumoral TReg Cells.
    Trends Cancer (IF 8.884) Pub Date : 2019-12-03
    Sara I Pai,Francesco M Marincola

    The immune landscape of cancer determines its responsiveness to immunotherapy. Tumors infiltrated with CD8+ T cells (immune-active tumors) are more likely to respond to immunomodulatory agents. However, immune activation often is counterbalanced by strong immunosuppressive mechanisms that are necessary to maintain homeostasis but consequentially can facilitate the survival of cancer cells in the immunocompetent

  • Regulatory Factor X 7 and its Potential Link to Lymphoid Cancers.
    Trends Cancer (IF 8.884) Pub Date : 2019-12-03
    Berenice A Fischer,Sonia T Chelbi,Greta Guarda

    Alterations in the Regulatory factor X 7 (RFX7) gene have recurrently been reported in lymphoid cancers. Uncharacterized until recently, this transcription factor regulates genes important for ciliogenesis and for limiting cellular metabolic activity. Here we discuss these observations and conjecture on the links between the reported functions of RFX7 and its potential role in lymphoid cancers, encouraging

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全球疫情及响应:BMC Medicine专题征稿