2,883 results match your criteria Cancer cell[Journal]


Telomere Stress Potentiates STING-Dependent Anti-tumor Immunity.

Cancer Cell 2020 Jun 10. Epub 2020 Jun 10.

Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390, USA.

Telomerase is an attractive target for anti-tumor therapy as it is almost universally expressed in cancer cells. Here, we show that treatment with a telomere-targeting drug, 6-thio-2'-deoxyguanosine (6-thio-dG), leads to tumor regression through innate and adaptive immune-dependent responses in syngeneic and humanized mouse models of telomerase-expressing cancers. 6-thio-dG treatment causes telomere-associated DNA damages that are sensed by dendritic cells (DCs) and activates the host cytosolic DNA sensing STING/interferon I pathway, resulting in enhanced cross-priming capacity of DCs and tumor-specific CD8 T cell activation. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.020DOI Listing

SETD2 Restricts Prostate Cancer Metastasis by Integrating EZH2 and AMPK Signaling Pathways.

Cancer Cell 2020 Jun 11. Epub 2020 Jun 11.

CAS Key Laboratory of Tissue Microenvironment and Tumor, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China; Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing 400042, China. Electronic address:

The level of SETD2-mediated H3K36me3 is inversely correlated with that of EZH2-catalyzed H3K27me3. Nevertheless, it remains unclear whether these two enzymatic activities are molecularly intertwined. Here, we report that SETD2 delays prostate cancer (PCa) metastasis via its substrate EZH2. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.022DOI Listing

PKCλ/ι Loss Induces Autophagy, Oxidative Phosphorylation, and NRF2 to Promote Liver Cancer Progression.

Cancer Cell 2020 Jun 9. Epub 2020 Jun 9.

Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA. Electronic address:

Oxidative stress plays a critical role in liver tissue damage and in hepatocellular carcinoma (HCC) initiation and progression. However, the mechanisms that regulate autophagy and metabolic reprogramming during reactive oxygen species (ROS) generation, and how ROS promote tumorigenesis, still need to be fully understood. We show that protein kinase C (PKC) λ/ι loss in hepatocytes promotes autophagy and oxidative phosphorylation. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.018DOI Listing

Selective Inhibition of STRN3-Containing PP2A Phosphatase Restores Hippo Tumor-Suppressor Activity in Gastric Cancer.

Cancer Cell 2020 Jun 10. Epub 2020 Jun 10.

State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China. Electronic address:

Loss of Hippo tumor-suppressor activity and hyperactivation of YAP are commonly observed in cancers. Inactivating mutations of Hippo kinases MST1/2 are uncommon, and it remains unclear how their activity is turned off during tumorigenesis. We identified STRN3 as an essential regulatory subunit of protein phosphatase 2A (PP2A) that recruits MST1/2 and promotes its dephosphorylation, which results in YAP activation. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.019DOI Listing

Altered RNA Splicing by Mutant p53 Activates Oncogenic RAS Signaling in Pancreatic Cancer.

Cancer Cell 2020 Jun 2. Epub 2020 Jun 2.

David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Dartmouth Norris Cotton Cancer Center, Lebanon, NH 03766, USA. Electronic address:

Pancreatic ductal adenocarcinoma (PDAC) is driven by co-existing mutations in KRAS and TP53. However, how these mutations collaborate to promote this cancer is unknown. Here, we uncover sequence-specific changes in RNA splicing enforced by mutant p53 which enhance KRAS activity. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.010DOI Listing
June 2020
23.523 Impact Factor

Targeting RSPO3-LGR4 Signaling for Leukemia Stem Cell Eradication in Acute Myeloid Leukemia.

Cancer Cell 2020 Jun 1. Epub 2020 Jun 1.

Cancer and Stem Cell Biology Group, Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address:

Signals driving aberrant self-renewal in the heterogeneous leukemia stem cell (LSC) pool determine aggressiveness of acute myeloid leukemia (AML). We report that a positive modulator of canonical WNT signaling pathway, RSPO-LGR4, upregulates key self-renewal genes and is essential for LSC self-renewal in a subset of AML. RSPO2/3 serve as stem cell growth factors to block differentiation and promote proliferation of primary AML patient blasts. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.014DOI Listing
June 2020
23.523 Impact Factor

Unbiased Proteomic Profiling Uncovers a Targetable GNAS/PKA/PP2A Axis in Small Cell Lung Cancer Stem Cells.

Cancer Cell 2020 May 22. Epub 2020 May 22.

Department of Pediatrics, Stanford University, 265 Campus Drive, Stanford, CA 94305-5457, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA. Electronic address:

Using unbiased kinase profiling, we identified protein kinase A (PKA) as an active kinase in small cell lung cancer (SCLC). Inhibition of PKA activity genetically, or pharmacologically by activation of the PP2A phosphatase, suppresses SCLC expansion in culture and in vivo. Conversely, GNAS (G-protein α subunit), a PKA activator that is genetically activated in a small subset of human SCLC, promotes SCLC development. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.003DOI Listing

Clinically Actionable Strategies for Studying Neural Influences in Cancer.

Cancer Cell 2020 Jun 11. Epub 2020 Jun 11.

Center for Neuroscience at the University of Pittsburgh, Pittsburgh Center for Pain Research and Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Neuro-glial activation is a recently identified hallmark of growing cancers. Targeting tumor hyperinnervation in preclinical and small clinical trials has yielded promising antitumor effects, highlighting the need of systematic analysis of neural influences in cancer (NIC). Here, we outline the strategies translating these findings from bench to the clinic. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.023DOI Listing
June 2020
23.523 Impact Factor

Pan-Cancer Early Detection: Hype or Hope?

Cancer Cell 2020 Jun 11. Epub 2020 Jun 11.

McCombs Institute for Cancer Early Detection and Treatment, Department of Clinical Cancer Prevention, MD Anderson Cancer Center, Houston, TX 77030, USA.

Universal cancer screening based on circulating DNA, proteins, metabolites, or other combinations has the potential to revolutionize early cancer detection, especially for cancers with no available screening modalities. Two recent publications in Science and Annals of Oncology highlight the potential benefits and limitations of single-test, multiple cancer screens. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.021DOI Listing

Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion.

Cancer Cell 2020 May 13. Epub 2020 May 13.

Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; City of Hope Comprehensive Cancer Center and Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA 91010, USA. Electronic address:

Fat mass and obesity-associated protein (FTO), an RNA N-methyladenosine (mA) demethylase, plays oncogenic roles in various cancers, presenting an opportunity for the development of effective targeted therapeutics. Here, we report two potent small-molecule FTO inhibitors that exhibit strong anti-tumor effects in multiple types of cancers. We show that genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especially LILRB4. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.04.017DOI Listing
May 2020
23.523 Impact Factor

Multi-phenotype CRISPR-Cas9 Screen Identifies p38 Kinase as a Target for Adoptive Immunotherapies.

Cancer Cell 2020 Jun;37(6):818-833.e9

Surgery Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Center for Cell-based Therapy, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA; Immunology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

T cells are central to all currently effective cancer immunotherapies, but the characteristics defining therapeutically effective anti-tumor T cells have not been comprehensively elucidated. Here, we delineate four phenotypic qualities of effective anti-tumor T cells: cell expansion, differentiation, oxidative stress, and genomic stress. Using a CRISPR-Cas9-based genetic screen of primary T cells we measured the multi-phenotypic impact of disrupting 25 T cell receptor-driven kinases. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.004DOI Listing

Reduction of Liver Metastasis Stiffness Improves Response to Bevacizumab in Metastatic Colorectal Cancer.

Cancer Cell 2020 Jun;37(6):800-817.e7

Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, University Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. Electronic address:

Tumors are influenced by the mechanical properties of their microenvironment. Using patient samples and atomic force microscopy, we found that tissue stiffness is higher in liver metastases than in primary colorectal tumors. Highly activated metastasis-associated fibroblasts increase tissue stiffness, which enhances angiogenesis and anti-angiogenic therapy resistance. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.005DOI Listing

Visualizing Synaptic Transfer of Tumor Antigens among Dendritic Cells.

Cancer Cell 2020 Jun;37(6):786-799.e5

Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA. Electronic address:

Generation of tumor-infiltrating lymphocytes begins when tumor antigens reach the lymph node (LN) to stimulate T cells, yet we know little of how tumor material is disseminated among the large variety of antigen-presenting dendritic cell (DC) subsets in the LN. Here, we demonstrate that tumor proteins are carried to the LN within discrete vesicles inside DCs and are then transferred among DC subsets. A synapse is formed between interacting DCs and vesicle transfer takes place in the absence of free exosomes. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.002DOI Listing

Selective Targeting of Different Bromodomains by Small Molecules.

Authors:
Jun Qi Yang Shi

Cancer Cell 2020 Jun;37(6):764-766

Division of Newborn Medicine and Epigenetics Program, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Department of Cell Biology, Harvard Medical School, Boston, MA, USA. Electronic address:

Two papers, published in Science and Nature, report inhibitiors selectively targeting distinct bromodomains of BET proteins. These advanced chemical tools facilitate functional understanding of epigenetic regulators in normal and disease states and enable development of new medicine potentially with lower toxicity. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.016DOI Listing

CAR T Cells for Mantle Cell Lymphoma: Is it Time to Reshuffle the Deck?

Cancer Cell 2020 Jun;37(6):761-763

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Center for Cell Engineering and Cellular Therapeutics Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.

In the New England Journal of Medicine, Wang et al. report favorable ZUMA-2 trial results of CAR T cells for patients with relapsed and refractory mantle cell lymphoma following prior failed Bruton's tyrosine kinase inhibitor therapy, with an overall response rate of 93% and an expected safety profile. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.015DOI Listing

p38 Kinase: A Key Target for Driving Potent T Cells for Adoptive Immunotherapy.

Cancer Cell 2020 Jun;37(6):756-758

Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia; Department of Pathology, University of Melbourne, Parkville, VIC, Australia; Department of Immunology, Monash University, Clayton, VIC, Australia. Electronic address:

In this issue of Cancer Cell, Gurusamy et al. use a CRISPR-Cas9 screening approach to demonstrate that deletion of p38 increases multiple phenotypic qualities of effective anti-tumor T cells. Preconditioning T cells with a p38 inhibitor enhances anti-tumor efficacy of adoptive immunotherapy. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.012DOI Listing

Targeting Tissue Stiffness in Metastasis: Mechanomedicine Improves Cancer Therapy.

Cancer Cell 2020 Jun;37(6):754-755

Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA. Electronic address:

Tissue stiffening plays a critical role in cancer progression. In this issue of Cancer Cell, Shen et al. demonstrated that highly activated fibroblasts in metastatic colorectal cancer increase tissue stiffness and angiogenesis. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.011DOI Listing
June 2020
23.523 Impact Factor

Cross-Presentation of Tumor Antigens Is Ruled by Synaptic Transfer of Vesicles among Dendritic Cell Subsets.

Cancer Cell 2020 Jun;37(6):751-753

The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA; Parker Institute of Cancer Immunotherapy, San Francisco, CA 94129, USA. Electronic address:

Migratory dendritic cells (DCs) in tumors transport antigens and share them with lymph node resident DCs through cross-presentation. In this issue of Cancer Cell, Ruhland et al. demonstrate that transport and transfer of tumor antigens in vesicles is a dominant pathway to load resident DCs for presentation to T cells. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.013DOI Listing

Translating Basic Cancer Discoveries to the Clinic.

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Cancer Cell 2020 Jun;37(6):735-737

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http://dx.doi.org/10.1016/j.ccell.2020.05.017DOI Listing

MYC Drives Temporal Evolution of Small Cell Lung Cancer Subtypes by Reprogramming Neuroendocrine Fate.

Cancer Cell 2020 May 30. Epub 2020 May 30.

Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA. Electronic address:

Small cell lung cancer (SCLC) is a neuroendocrine tumor treated clinically as a single disease with poor outcomes. Distinct SCLC molecular subtypes have been defined based on expression of ASCL1, NEUROD1, POU2F3, or YAP1. Here, we use mouse and human models with a time-series single-cell transcriptome analysis to reveal that MYC drives dynamic evolution of SCLC subtypes. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.001DOI Listing

MAX Functions as a Tumor Suppressor and Rewires Metabolism in Small Cell Lung Cancer.

Cancer Cell 2020 May 13. Epub 2020 May 13.

Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle, WA 98109, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Electronic address:

Small cell lung cancer (SCLC) is a highly aggressive and lethal neoplasm. To identify candidate tumor suppressors we applied CRISPR/Cas9 gene inactivation screens to a cellular model of early-stage SCLC. Among the top hits was MAX, the obligate heterodimerization partner for MYC family proteins that is mutated in human SCLC. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.04.016DOI Listing

Seeking Cellular Fitness and Immune Evasion: Autophagy in Pancreatic Carcinoma.

Cancer Cell 2020 Jun 28;37(6):759-760. Epub 2020 May 28.

Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China; Faculty of Medicine, Université Paris Saclay, Le Kremlin-Bicêtre, France; Gustave Roussy Comprehensive Cancer Institute, Villejuif, France; INSERM U1015, Villejuif, France; Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France. Electronic address:

In a recent Nature paper, Yamamoto et al. demonstrate that, in the particular context of pancreatic carcinoma, autophagy causes the continuous destruction of major histocompatibility complex class I (MHC-I) proteins. Suppression of autophagy favors MHC-I re-appearance on the surface of malignant cells, facilitating their clearance by cytotoxic T lymphocytes. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.009DOI Listing

Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia.

Cancer Cell 2020 Jun 28;37(6):867-882.e12. Epub 2020 May 28.

Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura & Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA. Electronic address:

A subset of B cell acute lymphoblastic leukemia (B-ALL) patients will relapse and succumb to therapy-resistant disease. The bone marrow microenvironment may support B-ALL progression and treatment evasion. Utilizing single-cell approaches, we demonstrate B-ALL bone marrow immune microenvironment remodeling upon disease initiation and subsequent re-emergence during conventional chemotherapy. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.04.015DOI Listing
June 2020
23.523 Impact Factor

The COVID-19 and Cancer Consortium: A Collaborative Effort to Understand the Effects of COVID-19 on Patients with Cancer.

Cancer Cell 2020 06 29;37(6):738-741. Epub 2020 Apr 29.

Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address:

National and international consortia will play a key role in understanding the effects of the coronavirus disease 2019 (COVID-19) pandemic on cancer patients. The COVID-19 and Cancer Consortium (CCC19) aims to collect and analyze observational data at scale to inform clinical practice in real-time. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.04.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188629PMC

SETD5-Coordinated Chromatin Reprogramming Regulates Adaptive Resistance to Targeted Pancreatic Cancer Therapy.

Cancer Cell 2020 Jun 21;37(6):834-849.e13. Epub 2020 May 21.

Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address:

Molecular mechanisms underlying adaptive targeted therapy resistance in pancreatic ductal adenocarcinoma (PDAC) are poorly understood. Here, we identify SETD5 as a major driver of PDAC resistance to MEK1/2 inhibition (MEKi). SETD5 is induced by MEKi resistance and its deletion restores refractory PDAC vulnerability to MEKi therapy in mouse models and patient-derived xenografts. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.04.014DOI Listing

Isotype Switching Converts Anti-CD40 Antagonism to Agonism to Elicit Potent Antitumor Activity.

Cancer Cell 2020 Jun 21;37(6):850-866.e7. Epub 2020 May 21.

Antibody and Vaccine Group, Cancer Sciences Unit, University of Southampton Faculty of Medicine, Southampton, UK; Institute for Life Sciences, University of Southampton, Southampton, UK. Electronic address:

Anti-CD40 monoclonal antibodies (mAbs) comprise agonists and antagonists, which display promising therapeutic activities in cancer and autoimmunity, respectively. We previously showed that epitope and isotype interact to deliver optimal agonistic anti-CD40 mAbs. The impact of Fc engineering on antagonists, however, remains largely unexplored. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280789PMC

Functional Genomics for Cancer Drug Target Discovery.

Cancer Cell 2020 May 15. Epub 2020 May 15.

Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel 4070, Switzerland. Electronic address:

Functional genomics describes a field of biology that uses a range of approaches for assessing gene function with high-throughput molecular, genetic, and cellular technologies. The near limitless potential for applying these concepts to study the activities of all genetic loci has completely upended how today's cancer biologists tackle drug target discovery. We provide an overview of contemporary functional genomics platforms, highlighting areas of distinction and complementarity across technologies, so as to aid in the development or interpretation of cancer-focused screening efforts. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.04.006DOI Listing

NCI's Work to Advance Cancer Research while Responding to the COVID-19 Pandemic.

Authors:
Dinah S Singer

Cancer Cell 2020 06 16;37(6):746-748. Epub 2020 May 16.

National Cancer Institute, National Instiutes of Health, Bethesda, MD 20892, USA. Electronic address:

During the COVID-19 pandemic, the National Cancer Institute (NCI) is bringing to bear its considerable expertise and capabilities to understand, treat, and prevent the disease. While responding to the pandemic, NCI's priority remains the advancement of cancer research. NCI has implemented many flexibilities for grantees and trainees. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229957PMC

TERAVOLT: Thoracic Cancers International COVID-19 Collaboration.

Cancer Cell 2020 06 16;37(6):742-745. Epub 2020 May 16.

Department of Medicine, Division of Hematology & Oncology, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address:

Prior publications on small subsets of cancer patients infected with SARS CoV-2 have shown an increased risk of mortality compared to the general population. Furthermore, patients with thoracic malignancies are thought to be at particularly high risk given their older age, smoking habits, and pre-existing cardio-pulmonary comorbidities. For this reason, physicians around the world have formed TERAVOLT, a global consortium dedicated to understanding the impact of COVID-19 on patients with thoracic malignancies. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229923PMC

Dietary Approaches to Cancer Therapy.

Cancer Cell 2020 Jun 14;37(6):767-785. Epub 2020 May 14.

The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address:

The concept that dietary changes could improve the response to cancer therapy is extremely attractive to many patients, who are highly motivated to take control of at least some aspect of their treatment. Growing insight into cancer metabolism is highlighting the importance of nutrient supply to tumor development and therapeutic response. Cancers show diverse metabolic requirements, influenced by factors such as tissue of origin, microenvironment, and genetics. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.04.005DOI Listing

Cancer Patient Care during COVID-19.

Cancer Cell 2020 06 14;37(6):749-750. Epub 2020 May 14.

St. George's Hospital Medical School, University of London, London, UK.

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http://dx.doi.org/10.1016/j.ccell.2020.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221386PMC

Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response.

Cancer Cell 2020 May;37(5):655-673.e11

Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA. Electronic address:

Follicular lymphomas (FLs) are slow-growing, indolent tumors containing extensive follicular dendritic cell (FDC) networks and recurrent EZH2 gain-of-function mutations. Paradoxically, FLs originate from highly proliferative germinal center (GC) B cells with proliferation strictly dependent on interactions with T follicular helper cells. Herein, we show that EZH2 mutations initiate FL by attenuating GC B cell requirement for T cell help and driving slow expansion of GC centrocytes that become enmeshed with and dependent on FDCs. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298875PMC

Comprehensive Analysis of Genetic Ancestry and Its Molecular Correlates in Cancer.

Cancer Cell 2020 May;37(5):639-654.e6

The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address:

We evaluated ancestry effects on mutation rates, DNA methylation, and mRNA and miRNA expression among 10,678 patients across 33 cancer types from The Cancer Genome Atlas. We demonstrated that cancer subtypes and ancestry-related technical artifacts are important confounders that have been insufficiently accounted for. Once accounted for, ancestry-associated differences spanned all molecular features and hundreds of genes. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.04.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328015PMC
May 2020
23.523 Impact Factor

Cancer Research after COVID-19: Where Do We Go from Here?

Cancer Cell 2020 05;37(5):637-638

The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:

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http://dx.doi.org/10.1016/j.ccell.2020.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212941PMC

The Glioma Stem Cell Model in the Era of Single-Cell Genomics.

Cancer Cell 2020 May;37(5):630-636

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 761001, Israel. Electronic address:

Glioma stem cells (GSCs) are thought to underlie glioma initiation, evolution, and resistance to existing therapies. Although functional evidence for GSCs is abundant, tumor heterogeneity and intrinsic limitations in GSC assays have represented barriers for the field. In this perspective, we revisit the GSC model in light of recent single-cell expression profiling studies. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.04.001DOI Listing

Screening for the Next-Generation T Cell Therapies.

Authors:
Jun Guo Chenqi Xu

Cancer Cell 2020 May;37(5):627-629

State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China; School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China. Electronic address:

In a recently published Cell paper, Roth et al. report a CRISPR-based platform for developing T cell therapies that strategically combine a tumor-specific TCR with novel protein factors that potentiate antitumor function. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.04.009DOI Listing

Microbial Diagnostics for Cancer: A Step Forward but Not Prime Time Yet.

Cancer Cell 2020 May;37(5):625-627

Departments of Biomedical Engineering, Computer Science, and Biostatistics, Johns Hopkins University, Baltimore, MD 21211, USA. Electronic address:

Translational microbiome science in humans has not yet fully realized its clinical potentials. The analyses by Poore et al. in Nature offer a strong foundation on which to begin to build microbial diagnostics to detect cancer. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.04.010DOI Listing

Expanding the Role for Immunotherapy in Triple-Negative Breast Cancer.

Cancer Cell 2020 May;37(5):623-624

Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia. Electronic address:

PD-1 axis blockade, in combination with chemotherapy, improves outcomes in advanced triple-negative breast cancer that is PD-L1 positive. The phase 3 KEYNOTE-522 trial now shows that the addition of pembrolizumab to chemotherapy improves pathological complete response rates regardless of PD-L1 status and appears to improve survival. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.04.007DOI Listing

Genetic Alterations Impact Immune Microenvironment Interactions in Follicular Lymphoma.

Cancer Cell 2020 May;37(5):621-622

Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland. Electronic address:

Interactions between germinal center B cells and immune cells in the microenvironment can play integral roles in transformation and growth of follicular lymphoma (FL). Three recent studies, two in this issue of Cancer Cell and one in Cell Reports, elucidate how genetic alterations in CTSS and EZH2 impact these interactions, with implications for FL immunotherapy. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.04.008DOI Listing

Bridging the Gap: The Impact of Genetic Ancestry on Routes to Tumorigenesis.

Cancer Cell 2020 May;37(5):619-621

Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA. Electronic address:

Whether ancestry drives molecular differences that underlie disparities in cancer incidence and outcome is poorly understood. In this issue of Cancer Cell, Carrot-Zhang et al., through a rigorous analytical framework, explore ancestry-specific patterns of molecular alterations in cancers and demonstrate the need for novel strategies to address this formidable challenge. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.04.011DOI Listing

Comprehensive Molecular Characterization Identifies Distinct Genomic and Immune Hallmarks of Renal Medullary Carcinoma.

Cancer Cell 2020 May 30;37(5):720-734.e13. Epub 2020 Apr 30.

Department of Genitourinary Medical Oncology, Unit 1374, The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, Houston, TX 77030-3721, USA. Electronic address:

Renal medullary carcinoma (RMC) is a highly lethal malignancy that mainly afflicts young individuals of African descent and is resistant to all targeted agents used to treat other renal cell carcinomas. Comprehensive genomic and transcriptomic profiling of untreated primary RMC tissues was performed to elucidate the molecular landscape of these tumors. We found that RMC was characterized by high replication stress and an abundance of focal copy-number alterations associated with activation of the stimulator of the cyclic GMP-AMP synthase interferon genes (cGAS-STING) innate immune pathway. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288373PMC

Cathepsin S Regulates Antigen Processing and T Cell Activity in Non-Hodgkin Lymphoma.

Cancer Cell 2020 May 23;37(5):674-689.e12. Epub 2020 Apr 23.

Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, EPFL, Lausanne, 1015 Switzerland; Swiss Cancer Center Leman (SCCL), Lausanne, 1015 Switzerland. Electronic address:

Genomic alterations in cancer cells can influence the immune system to favor tumor growth. In non-Hodgkin lymphoma, physiological interactions between B cells and the germinal center microenvironment are coopted to sustain cancer cell proliferation. We found that follicular lymphoma patients harbor a recurrent hotspot mutation targeting tyrosine 132 (Y132D) in cathepsin S (CTSS) that enhances protein activity. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.03.016DOI Listing

C/EBPα and GATA-2 Mutations Induce Bilineage Acute Erythroid Leukemia through Transformation of a Neomorphic Neutrophil-Erythroid Progenitor.

Cancer Cell 2020 May 23;37(5):690-704.e8. Epub 2020 Apr 23.

MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK. Electronic address:

Acute erythroid leukemia (AEL) commonly involves both myeloid and erythroid lineage transformation. However, the mutations that cause AEL and the cell(s) that sustain the bilineage leukemia phenotype remain unknown. We here show that combined biallelic Cebpa and Gata2 zinc finger-1 (ZnF1) mutations cooperatively induce bilineage AEL, and that the major leukemia-initiating cell (LIC) population has a neutrophil-monocyte progenitor (NMP) phenotype. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.03.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218711PMC

Integrated Molecular and Clinical Analysis of 1,000 Pediatric Low-Grade Gliomas.

Cancer Cell 2020 Apr;37(4):569-583.e5

Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Pathology, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address:

Pediatric low-grade gliomas (pLGG) are frequently driven by genetic alterations in the RAS-mitogen-activated protein kinase (RAS/MAPK) pathway yet show unexplained variability in their clinical outcome. To address this, we characterized a cohort of >1,000 clinically annotated pLGG. Eighty-four percent of cases harbored a driver alteration, while those without an identified alteration also often exhibited upregulation of the RAS/MAPK pathway. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.03.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169997PMC

A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications.

Cancer Cell 2020 Apr;37(4):551-568.e14

Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:

The development of precision medicine approaches for diffuse large B cell lymphoma (DLBCL) is confounded by its pronounced genetic, phenotypic, and clinical heterogeneity. Recent multiplatform genomic studies revealed the existence of genetic subtypes of DLBCL using clustering methodologies. Here, we describe an algorithm that determines the probability that a patient's lymphoma belongs to one of seven genetic subtypes based on its genetic features. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.03.015DOI Listing

Targeting the MAPK Pathway in KRAS-Driven Tumors.

Cancer Cell 2020 Apr;37(4):543-550

Molecular Oncology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain. Electronic address:

KRAS mutations occur in a quarter of all of human cancers, yet no selective drug has been approved to treat these tumors. Despite the recent development of drugs that block KRAS, the majority of KRAS oncoproteins remain undruggable. Here, we review recent efforts to validate individual components of the mitogen-activated protein kinase (MAPK) pathway as targets to treat KRAS-mutant cancers by comparing genetic information derived from experimental mouse models of KRAS-driven lung and pancreatic tumors with the outcome of selective MAPK inhibitors in clinical trials. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.03.013DOI Listing

Response and Resistance to BCR-ABL1-Targeted Therapies.

Cancer Cell 2020 Apr;37(4):530-542

Division of Hematology/Medical Oncology, Knight Cancer Insitute, Oregon Health & Science University, Portland, OR, USA.

Chronic myeloid leukemia (CML), caused by constitutively active BCR-ABL1 fusion tyrosine kinase, has served as a paradigm for successful application of molecularly targeted cancer therapy. The development of the tyrosine kinase inhibitor (TKI) imatinib allows patients with CML to experience near-normal life expectancy. Specific point mutations that decrease drug binding affinity can produce TKI resistance, and second- and third-generation TKIs largely mitigate this problem. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.03.006DOI Listing

Mechanisms of Sensitivity and Resistance to CDK4/6 Inhibition.

Cancer Cell 2020 Apr;37(4):514-529

Cell Division and Cancer Group, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain. Electronic address:

Inhibiting the cell-cycle kinases CDK4 and CDK6 results in significant therapeutic effect in patients with advanced hormone-positive breast cancer. The efficacy of this strategy is, however, limited by innate or acquired resistance mechanisms and its application to other tumor types is still uncertain. Here, through an integrative analysis of sensitivity and resistance mechanisms, we discuss the use of CDK4/6 inhibitors in combination with available targeted therapies, immunotherapy, or classical chemotherapy with the aim of improving future therapeutic uses of CDK4/6 inhibition in a variety of cancers. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.03.010DOI Listing

Overcoming Endocrine Resistance in Breast Cancer.

Cancer Cell 2020 Apr;37(4):496-513

Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:

Estrogen receptor-positive (ER) breast cancer is the most common breast cancer subtype. Treatment of ER breast cancer comprises interventions that suppress estrogen production and/or target the ER directly (overall labeled as endocrine therapy). While endocrine therapy has considerably reduced recurrence and mortality from breast cancer, de novo and acquired resistance to this treatment remains a major challenge. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.03.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169993PMC

Liquid Biopsy-Based Biomarkers of Treatment Response and Resistance.

Cancer Cell 2020 Apr;37(4):485-495

Cancer Research UK Manchester Institute Cancer Biomarker Centre, University of Manchester, Alderley Park, Macclesfield SK10 4TG, UK; Cancer Research UK Lung Cancer Centre of Excellence, University of Manchester, Oxford Road, Manchester M13 9PL, UK. Electronic address:

Predictive biomarkers aid selection of personalized therapy targeted to molecular alterations within an individual's tumor. Patients' responses to targeted therapies are commonly followed by treatment resistance. Here, we survey liquid biopsies as alternatives to tumor biopsies to assess predictive and therapy response biomarkers. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.03.012DOI Listing