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  • Managing Cancer Care during the COVID-19 Pandemic and Beyond.
    Trends Cancer (IF 11.093) Pub Date : 2020-04-27
    Omar Alhalabi,Vivek Subbiah

    The coronavirus disease 2019 (COVID-19) pandemic is posing insurmountable challenges to healthcare systems globally. Cancer therapy is complex, and outcomes are centered on timing. Many oncology societies and health ministries have issued guidelines for cancer care to enable oncologists and patients to navigate the crisis. Lessons learned should inform care models for future pandemics.

  • Tele-oncology in the COVID-19 Era: The Way Forward?
    Trends Cancer (IF 11.093) Pub Date : 2020-05-27
    Manasi Mahesh Shirke,Safwan Ahmed Shaikh,Amer Harky

    COVID-19 has had a devastating impact on the care of cancer patients. Thus, tele-oncology has become a necessity to improve cancer care. Several organisations have issued guidelines for its use during COVID-19. Despite certain shortcomings, tele-oncology has great potential to help cancer patients during COVID-19 and in the future.

  • Tissue-Specific Carcinogens as Soil to Seed BRCA1/2-Mutant Hereditary Cancers.
    Trends Cancer (IF 11.093) Pub Date : 2020-04-23
    Anup Kumar Singh,Xiaochun Yu

    Despite their ubiquitous expression, the inheritance of monoallelic germline mutations in breast cancer susceptibility gene type 1 or 2 (BRCA1/2) poses tissue-specific variations in cancer risks and primarily associate with familial breast and ovarian cancers. The molecular basis of this tissue-specific tumor incidence remains unknown and intriguing to cancer researchers. A plethora of recent reports

  • A Timeline of Immune Checkpoint Inhibitor Approvals in Small Cell Lung Cancer
    Trends Cancer (IF 11.093) Pub Date : 2020-06-29
    Jennifer Gill; Jeremy Paul Cetnar; Vinay Prasad

    In this commentary, we review the timeline of clinical trials and regulatory actions of approved immune checkpoint inhibitors for small cell lung cancer, discuss challenges faced by regulatory agencies, and highlight paradoxical lessons that emerge. Accelerated approvals may fail to expedite drugs to market in this setting and further research on overall survival benefit is needed to prove drug efficacy

  • Can Energetic Capacity Help Explain Why Physical Activity Reduces Cancer Risk?
    Trends Cancer (IF 11.093) Pub Date : 2020-06-26
    Peter A. Biro; Frédéric Thomas; Beata Ujvari; Christa Beckmann

    Increased physical activity reduces cancer risk in humans, but why this whole-organism attribute reduces cancer remains unclear. Active individuals tend to have high capacity to generate energy on a sustained basis, which in turn can permit greater immune responses crucial for fighting emerging neoplasia. Thus, we suggest energetic capacity as a potential mechanism to explain the activity–cancer link

  • Metronomic Maintenance for High-Risk Pediatric Malignancies: One Size Will Not Fit All
    Trends Cancer (IF 11.093) Pub Date : 2020-06-26
    Nicolas André; Daniel Orbach; Eddy Pasquier

    Maintenance therapy sometimes relies on the use of metronomic chemotherapy (MC); that is, the continuous administration of low-dose chemotherapy. Maintenance therapy has been successfully used for decades in pediatric patients with acute lymphoblastic leukemia (ALL) and recent results have demonstrated improved outcomes in patients with pediatric high-risk rhabdomyosarcoma (RMS) on maintenance therapy

  • Clinical Development of BRAF plus MEK Inhibitor Combinations.
    Trends Cancer (IF 11.093) Pub Date : 2020-06-13
    Vivek Subbiah,Christina Baik,John M Kirkwood

    Genomic profiling shows that many solid tumors are characterized by specific driver aberrations, and this has expanded the therapeutic options for many patients. The mitogen-activated protein kinase (MAPK) pathway is a key cell signaling pathway involved in regulating cellular growth, proliferation, and survival. Driver mutations in the BRAF gene, a key player in the MAPK pathway, are described in

  • Unfolded Protein Response in Leukemia: From Basic Understanding to Therapeutic Opportunities.
    Trends Cancer (IF 11.093) Pub Date : 2020-06-13
    Ali Khateb,Ze'ev A Ronai

    Understanding genetic and epigenetic changes that underlie abnormal proliferation of hematopoietic stem and progenitor cells is critical for development of new approaches to monitor and treat leukemia. The unfolded protein response (UPR) is a conserved adaptive signaling pathway that governs protein folding, secretion, and energy production and serves to maintain protein homeostasis in various cellular

  • Why Great Mitotic Inhibitors Make Poor Cancer Drugs.
    Trends Cancer (IF 11.093) Pub Date : 2020-06-11
    Victoria C Yan,Hannah E Butterfield,Anton H Poral,Matthew J Yan,Kristine L Yang,Cong-Dat Pham,Florian L Muller

    Chemotherapy is central to oncology, perceived to operate only on prolific cancerous tissue. Yet, many non-neoplastic tissues are more prolific compared with typical tumors. Chemotherapies achieve sufficient therapeutic windows to exert antineoplastic activity because they are prodrugs that are bioactivated in cancer-specific environments. The advent of precision medicine has obscured this concept

  • Advanced Prostate Cancer: Treatment Advances and Future Directions.
    Trends Cancer (IF 11.093) Pub Date : 2020-06-10
    Umang Swami,Taylor R McFarland,Roberto Nussenzveig,Neeraj Agarwal

    Prostate cancer affects one in every nine men in the USA and is the second leading cause of cancer-related death. The treatment landscape of advanced prostate cancer is changing rapidly. Multiple agents including abiraterone, enzalutamide, apalutamide, darolutamide, docetaxel, cabazitaxel, radium-223, and sipuleucel-T have been approved for advanced prostate cancer. Appropriate drug selection remains

  • PML Nuclear Body Biogenesis, Carcinogenesis, and Targeted Therapy.
    Trends Cancer (IF 11.093) Pub Date : 2020-06-08
    Yuwen Li,Xiaodan Ma,Wenyu Wu,Zhu Chen,Guoyu Meng

    Targeted therapy has become increasingly important in cancer therapy. For example, targeting the promyelocytic leukemia PML protein in leukemia has proved to be an effective treatment. PML is the core component of super-assembled structures called PML nuclear bodies (NBs). Although this nuclear megaDalton complex was first observed in the 1960s, the mechanism of its assembly remains poorly understood

  • DNA Damage Repair Deficiency in Prostate Cancer.
    Trends Cancer (IF 11.093) Pub Date : 2020-06-06
    Susanne Burdak-Rothkamm,Wael Y Mansour,Kai Rothkamm

    Molecular-targeted therapies and treatment stratification based on molecular biomarkers have rapidly gained momentum in the therapeutic spectrum for patients with prostate cancer, particularly those with aggressive disease. DNA damage repair (DDR) pathways are commonly impaired in prostate cancer. Recent studies have detailed mechanisms interconnecting the DDR with the androgen receptor (AR) signaling

  • Molecular Tumor Boards in Clinical Practice.
    Trends Cancer (IF 11.093) Pub Date : 2020-06-06
    Claudio Luchini,Rita T Lawlor,Michele Milella,Aldo Scarpa

    Next-generation sequencing (NGS) application in clinical practice requires the implementation of molecular tumor boards (MTBs). Starting from a systematic review of literature, we discuss the MTB-related key points: MTB aims and composition, types of tumors to discuss, types of molecular analyses, methods for classifying actionability, appropriate turnaround time, and cost management.

  • Genomic Instability in Multiple Myeloma.
    Trends Cancer (IF 11.093) Pub Date : 2020-05-30
    David A Alagpulinsa,Raphael E Szalat,Mark C Poznansky,Robert J Shmookler Reis

    Genomic instability (GIN), an increased tendency to acquire genomic alterations, is a cancer hallmark. However, its frequency, underlying causes, and disease relevance vary across different cancers. Multiple myeloma (MM), a plasma cell malignancy, evolves through premalignant phases characterized by genomic abnormalities. Next-generation sequencing (NGS) methods are deconstructing the genomic landscape

  • Senescent Cells in Cancer Therapy: Friends or Foes?
    Trends Cancer (IF 11.093) Pub Date : 2020-05-29
    Boshi Wang,Jaskaren Kohli,Marco Demaria

    Several cancer interventions induce DNA damage and promote senescence in cancer and nonmalignant cells. Senescent cells secrete a collection of proinflammatory factors collectively termed the senescence-associated secretory phenotype (SASP). SASP factors are able to potentiate various aspects of tumorigenesis, including proliferation, metastasis, and immunosuppression. Moreover, the accumulation and

  • Tunneling Nanotubes: The Fuel of Tumor Progression?
    Trends Cancer (IF 11.093) Pub Date : 2020-05-26
    Giulia Pinto,Christel Brou,Chiara Zurzolo

    Tunneling nanotubes (TNTs) are thin membrane tubes connecting remote cells and allowing the transfer of cellular content. TNTs have been reported in several cancer in vitro, ex vivo, and in vivo models. Cancer cells exploit TNT-like connections to exchange material between themselves or with the tumoral microenvironment. Cells acquire new abilities (e.g., enhanced metabolic plasticity, migratory phenotypes

  • Multiplex Spatial Bioimaging for Combination Therapy Design.
    Trends Cancer (IF 11.093) Pub Date : 2020-05-25
    Shuangyi Cai,Mayar Allam,Ahmet F Coskun

    Multiplex spatial analyses dissect the heterogeneous cellular abundances and interactions in tumors. Single-cell bioimaging profiles many disease-associated protein biomarkers in patient biopsies to inform the design of cancer therapies. Guided by the mechanistic insights from spatial cellular maps, combination therapy can efficiently eliminate cancers with reduced off-targets, resistance, and relapse

  • Mitochondrial Stress Response and Cancer.
    Trends Cancer (IF 11.093) Pub Date : 2020-05-22
    Jordan O'Malley,Rahul Kumar,Joseph Inigo,Nagendra Yadava,Dhyan Chandra

    Cancer cells survive and adapt to many types of stress including hypoxia, nutrient deprivation, metabolic, and oxidative stress. These stresses are sensed by diverse cellular signaling processes, leading to either degradation of mitochondria or alleviation of mitochondrial stress. This review discusses signaling during sensing and mitigation of stress involving mitochondrial communication with the

  • Nanotherapeutics for Antimetastatic Treatment.
    Trends Cancer (IF 11.093) Pub Date : 2020-05-21
    Fujun Yang,Zhiqiang Zhao,Bingjun Sun,Qin Chen,Jin Sun,Zhonggui He,Cong Luo

    Tumor metastases, that is, the development of secondary tumors in organs distant from the primary tumor, and their treatment remain a serious problem in cancer therapy. The unique challenges for tracking and treating tumor metastases lie in the small size, high heterogeneity, and wide dispersion to distant organs of metastases. Recently, nanomedicines, with the capacity to precisely deliver therapeutic

  • The Hippo Pathway as a Driver of Select Human Cancers.
    Trends Cancer (IF 11.093) Pub Date : 2020-05-20
    Aishwarya Kulkarni,Matthew T Chang,Joseph H A Vissers,Anwesha Dey,Kieran F Harvey

    The Hippo pathway regulates myriad biological processes in diverse species and is a key cancer signaling network in humans. Although Hippo has been linked to multiple aspects of cancer, its role in this disease is incompletely understood. Large-scale pan-cancer analyses of core Hippo pathway genes reveal that the pathway is mutated at a high frequency only in select human cancers, including malignant

  • RNA Splicing and Cancer.
    Trends Cancer (IF 11.093) Pub Date : 2020-05-17
    Eric Wang,Iannis Aifantis

    RNA splicing is an essential process that governs many aspects of cellular proliferation, survival, and differentiation. Considering the importance of RNA splicing in gene regulation, alterations in this pathway have been implicated in many human cancers. Large-scale genomic studies have uncovered a spectrum of splicing machinery mutations that contribute to tumorigenesis. Moreover, cancer cells are

  • Above and Beyond Cancer Therapy: Translating Biomaterials into the Clinic.
    Trends Cancer (IF 11.093) Pub Date : 2020-05-16
    João Conde

    Given extensive reports of anticancer nanomedicines in preclinical studies, why is there such a paucity of clinical trials using these therapies? Nanotechnology can certainly deliver, but we need to tackle the limitations that are impeding the translation of nanomedicines into the clinic and start benefiting from their full potential.

  • Carcinogens in Products: Inadequate Protections Raise Cancer Risks.
    Trends Cancer (IF 11.093) Pub Date : 2020-05-16
    Veena Singla

    Evidence shows, that over their life cycle, chemicals used in everyday products contribute to raising cancer risks, especially for vulnerable populations such as children and communities of color. This article outlines how US policies have not yet incorporated current science in relation to environmental carcinogenesis and recommends improvements to protect public health.

  • 3D Spheroids Propel Tumor Characterization.
    Trends Cancer (IF 11.093) Pub Date : 2020-05-15
    Shengli Li,Zhao Zhang,Leng Han

    Determining the functions of cancer driver genes in cancer models to mimic in vivo tumors has been a significant challenge. In a recent study, Han et al. implemented large-scale clustered regularly interspaced short palindromic repeats (CRISPR) screening in 3D lung cancer spheroids, revealing advantages of 3D spheroids over 2D monolayers, wherein novel therapeutic targets were identified, such as carboxypeptidase

  • Genes that Mediate Metastasis across the Blood-Brain Barrier.
    Trends Cancer (IF 11.093) Pub Date : 2020-05-13
    Jawad Fares,Deepak Kanojia,Aida Rashidi,Ilya Ulasov,Maciej S Lesniak

    Brain metastasis is an important cause of mortality in patients with cancer and represents the majority of all intracranial tumors. A key step during the metastatic journey of the cancer cell to the brain is the invasion through the blood-brain barrier (BBB). Nevertheless, the molecular mechanisms that govern this process remain unknown. The BBB has been blamed for limiting the access of therapeutic

  • NF-κB in the New Era of Cancer Therapy.
    Trends Cancer (IF 11.093) Pub Date : 2020-05-11
    Baptiste Eluard,Catherine Thieblemont,Véronique Baud

    Although mortality rates have declined in recent years, the majority of cancers remain incurable and the medical challenge is evident. Recent progress in cancer genetics and genomics along with the identification of a novel generation of cancer hallmarks, that is, reprogramming of energy metabolism and evasion from immune surveillance, have led to the discovery of novel NF-κB-dependent cancer vulnerabilities

  • Amyloid Evolvability and Cancer.
    Trends Cancer (IF 11.093) Pub Date : 2020-05-05
    Yoshiki Takamatsu,Gilbert Ho,Makoto Hashimoto

    p53 and γ-synuclein are two major regulators of cancer pathogenesis that have the propensity to form amyloid-like fibrils reminiscent of those in neurodegenerative diseases. Here we propose that fibril formation by these amyloidogenic molecules reflects evolvability, an acquired epigenetic inheritance that may be involved in cancer proliferation, drug resistance, and metastasis.

  • Targeting Glycosylation: A New Road for Cancer Drug Discovery.
    Trends Cancer (IF 11.093) Pub Date : 2020-05-04
    Ana Filipa Costa,Diana Campos,Celso A Reis,Catarina Gomes

    Cancer is a deadly disease that encompasses numerous cellular modifications. Among them, alterations in glycosylation are a proven reliable hallmark of cancer, with most biomarkers used in the clinic detecting cancer-associated glycans. Despite their clear potential as therapy targets, glycans have been overlooked in drug discovery strategies. The complexity associated with the glycosylation process

  • Cell Competition Spurs Selection of Aggressive Cancer Cells.
    Trends Cancer (IF 11.093) Pub Date : 2020-04-20
    Taylor Parker,Esha Madan,Kartik Gupta,Eduardo Moreno,Rajan Gogna

    Within heterogeneous tumors, cancer cells are constantly interacting. Cell competition (CC) is a fitness-based selection mechanism that results in increased proliferation of discrete populations at the expense of their less fit neighbors. CC-based selection of fit cells may also drive selection of the most aggressive cancer cells.

  • Zebrafish Xenografts for Drug Discovery and Personalized Medicine.
    Trends Cancer (IF 11.093) Pub Date : 2020-04-17
    Jerry Xiao,Eric Glasgow,Seema Agarwal

    Cancer is the second leading cause of death in the world. Given that cancer is a highly individualized disease, predicting the best chemotherapeutic treatment for individual patients can be difficult. Ex vivo models such as mouse patient-derived xenografts (PDX) and organoids are being developed to predict patient-specific chemosensitivity profiles before treatment in the clinic. Although promising

  • Emerging Mechanisms by which EMT Programs Control Stemness.
    Trends Cancer (IF 11.093) Pub Date : 2020-04-17
    Molly M Wilson,Robert A Weinberg,Jacqueline A Lees,Vincent J Guen

    Tissue regeneration relies on adult stem cells (SCs) that possess the ability to self-renew and produce differentiating progeny. In an analogous manner, the development of certain cancers depends on a subset of tumor cells, called cancer stem cells (CSCs), with SC-like properties. In addition to being responsible for tumorigenesis, CSCs exhibit elevated resistance to therapy and thus drive tumor relapse

  • Exosomes as a Multicomponent Biomarker Platform in Cancer.
    Trends Cancer (IF 11.093) Pub Date : 2020-04-16
    Valerie S LeBleu,Raghu Kalluri

    Cancer is a complex disease that is associated with genetic aberrations and subsequent cellular and noncellular host responses. Tumors harbor diverse cell types that engage in a dynamic interplay to sustain cancer-specific signaling networks. A component of such cellular communication is the production and exchange of various types of extracellular vesicle (EV). Exosomes are small EVs with growing

  • Janus Face of Drug-Induced Tetraploidy in Non-Hodgkin Lymphoma
    Trends Cancer (IF 11.093) Pub Date : 2020-04-11
    Daruka Mahadevan; Gregory C. Rogers

    Anticancer agents often cause drug-induced tetraploidy (DIT) in cancer cells. DIT is not only a mechanism of inherited drug resistance, but proliferating DIT cells can produce progeny with increased ploidy or aneuploid genomes that drive aggressive disease. Here, we explore combinatorial therapeutic strategies for either preventing or eliminating DIT cells.

  • Epigenetic Biomarkers in Gallbladder Cancer
    Trends Cancer (IF 11.093) Pub Date : 2020-04-11
    Pramod K. Tiwari

    Gallbladder cancer (GBC) is associated with various nongenetic and genetic factors. Lack of specific and sensitive diagnostic markers has significantly impacted the mortality of this disease. Here we discuss the recent discovery of epigenetic changes that show great promise as diagnostic biomarkers as well as potential therapeutic targets for GBC.

  • SPAG5: An Emerging Oncogene
    Trends Cancer (IF 11.093) Pub Date : 2020-04-11
    Ji He; Andrew R. Green; Yan Li; Stephen Y.T. Chan; Dong-Xu Liu

    Sperm-associated Antigen 5 (SPAG5) is a mitotic spindle protein. Recent studies have found that it is overexpressed in many human cancers and functions as an oncogene. Here, we summarize the current underlying mechanisms for its oncogenic roles in regulating cellular behaviors of cancer cells and discuss the possibility of targeting SPAG5 for cancer treatment.

  • Targeting TGFβ Signalling in Cancer: Toward Context-Specific Strategies
    Trends Cancer (IF 11.093) Pub Date : 2020-04-08
    Rhiannon French; Yuliang Feng; Siim Pauklin

    The transforming growth factor beta (TGFβ) signalling pathway regulates a range of important cellular processes in a context-dependent manner. Recent discoveries have provided important insights into the regulation of the TGFβ pathway and its change from an antitumorigenic to a protumorigenic pathway. These findings may have important implications for cancer stem cell (CSC) functions and therapeutic

  • Vitamin B6 Fuels Acute Myeloid Leukemia Growth
    Trends Cancer (IF 11.093) Pub Date : 2020-04-02
    Shuai Jiang

    Mounting evidence indicates that vitamins C and D are linked to tumor growth, but the relevance of vitamin B6 remains uncertain. In a recent study, Chen et al. demonstrate that pyridoxal kinase promotes vitamin B6 phosphorylation, producing the active form pyridoxal 5′-phosphate, which regulates two key metabolic enzymes required for acute myeloid leukemia (AML) cell growth.

  • Cancer Epigenetics, Tumor Immunity, and Immunotherapy
    Trends Cancer (IF 11.093) Pub Date : 2020-03-31
    Jian Cao; Qin Yan

    Epigenetic mechanisms, including DNA methylation, histone post-translational modifications, and chromatin structure regulation, are critical for the interactions between tumor and immune cells. Emerging evidence shows that tumors commonly hijack various epigenetic mechanisms to escape immune restriction. As a result, the pharmaceutical modulation of epigenetic regulators, including ‘writers’, ‘readers’

  • Novel Forms of Immunomodulation for Cancer Therapy.
    Trends Cancer (IF 11.093) Pub Date : 2020-03-31
    Alfonso Serrano-Del Valle,Javier Naval,Alberto Anel,Isabel Marzo

    In recent years immunotherapy has provided new hope for cancer patients. However, some patients eventually relapse. Immunological responses are thought to underlie the long-term effects of conventional or targeted therapies. Whether this influence emerges from direct effects on cancer cells through immunogenic cell death (ICD) or by modulating the immune environment requires further clarification.

  • Exosomal PD-L1: Roles in Tumor Progression and Immunotherapy
    Trends Cancer (IF 11.093) Pub Date : 2020-03-29
    Samantha M. Morrissey; Jun Yan

    The use of immune checkpoint therapies targeting programmed death-1 (PD-1) and its ligand (PD-L1) continue to show limited durable success in clinical cases despite widespread application. While some patients achieve complete responses and disease remission, others are completely resistant to the therapy. Recent evidence in the field suggests that tumor-derived exosomes could be responsible for mediating

  • MGMT Status as a Clinical Biomarker in Glioblastoma.
    Trends Cancer (IF 11.093) 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 11.093) 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 11.093) 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 11.093) 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 11.093) 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 11.093) 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 11.093) 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 11.093) 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 11.093) 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 11.093) 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 11.093) 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 11.093) 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 11.093) 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 11.093) 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 11.093) 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 11.093) 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 11.093) 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 11.093) 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 11.093) 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 11.093) 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.

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