当前期刊: Nature Cancer Go to current issue    加入关注   
显示样式:        排序: IF: - GO 导出
  • A single-domain bispecific antibody targeting CD1d and the NKT T-cell receptor induces a potent antitumor response
    Nat. Cancer Pub Date : 2020-09-14
    Roeland Lameris; Adam Shahine; Daniel G. Pellicci; Adam P. Uldrich; Stephanie Gras; Jérôme Le Nours; Richard W. J. Groen; Jana Vree; Scott J. J. Reddiex; Sergio M. Quiñones-Parra; Stewart K. Richardson; Amy R. Howell; Sonja Zweegman; Dale I. Godfrey; Tanja D. de Gruijl; Jamie Rossjohn; Hans J. van der Vliet

    Antibody-mediated modulation of major histocompatibility complex (MHC) molecules, or MHC class I-like molecules, could constitute an effective immunotherapeutic approach. We describe how single-domain antibodies (VHH), specific for the human MHC class I-like molecule CD1d, can modulate the function of CD1d-restricted T cells and how one VHH (1D12) specifically induced strong type I natural killer T

  • Illuminating the noncoding genome in cancer
    Nat. Cancer Pub Date : 2020-09-14
    Xiaoyang Zhang; Matthew Meyerson

    Understanding the mechanisms underlying tumorigenesis requires comprehensive annotation of the cancer genome. The majority of the human genome consists of noncoding regions, harboring functional elements that regulate the expression of protein-coding genes, including proto-oncogenes or tumor-suppressor genes. Technologies such as whole-genome and long-read sequencing provide powerful means to identify

  • Don’t shortchange public trust in science
    Nat. Cancer Pub Date : 2020-09-11

    The need to address COVID-19 is placing huge demands on biomedical research and regulatory processes. Under pressure, it is essential to uphold high bioethical principles and rigorous standards for the development and approval of medicines.

  • Dual ARID1A/ARID1B loss leads to rapid carcinogenesis and disruptive redistribution of BAF complexes
    Nat. Cancer Pub Date : 2020-09-07
    Zixi Wang; Kenian Chen; Yuemeng Jia; Jen-Chieh Chuang; Xuxu Sun; Yu-Hsuan Lin; Cemre Celen; Lin Li; Fang Huang; Xin Liu; Diego H. Castrillon; Tao Wang; Hao Zhu

    SWI/SNF chromatin remodelers play critical roles in development and cancer. The causal links between SWI/SNF complex disassembly and carcinogenesis are obscured by redundancy between paralogous components. Canonical BAF (cBAF)-specific paralogs ARID1A and ARID1B are synthetic lethal in some contexts, but simultaneous mutations in both ARID1s are prevalent in cancer. To understand if and how cBAF abrogation

  • Targeting purine synthesis in ASS1-expressing tumors enhances the response to immune checkpoint inhibitors
    Nat. Cancer Pub Date : 2020-08-31
    Rom Keshet; Joo Sang Lee; Lital Adler; Muhammed Iraqi; Yarden Ariav; Lisha Qiu Jin Lim; Shaul Lerner; Shiran Rabinovich; Roni Oren; Rotem Katzir; Hila Weiss Tishler; Noa Stettner; Omer Goldman; Hadas Landesman; Sivan Galai; Yael Kuperman; Yuri Kuznetsov; Alexander Brandis; Tevi Mehlman; Sergey Malitsky; Maxim Itkin; S. Eleonore Koehler; Yongmei Zhao; Keyur Talsania; Tsai-wei Shen; Nir Peled; Igor Ulitsky;

    Argininosuccinate synthase (ASS1) downregulation in different tumors has been shown to support cell proliferation and yet, in several common cancer subsets ASS1 expression associates with poor patient prognosis. Here we demonstrate that ASS1 expression under glucose deprivation is induced by c-MYC, providing survival benefit by increasing nitric oxide synthesis and activating the gluconeogenic enzymes

  • Publisher Correction: Keap1 mutation renders lung adenocarcinomas dependent on Slc33a1
    Nat. Cancer Pub Date : 2020-08-21
    Rodrigo Romero; Francisco J. Sánchez-Rivera; Peter M. K. Westcott; Kim L. Mercer; Arjun Bhutkar; Alexander Muir; Tania J. González Robles; Swanny Lamboy Rodríguez; Laura Z. Liao; Sheng Rong Ng; Leanne Li; Caterina I. Colón; Santiago Naranjo; Mary Clare Beytagh; Caroline A. Lewis; Peggy P. Hsu; Roderick T. Bronson; Matthew G. Vander Heiden; Tyler Jacks

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

  • Super-sonic speed of DNA synthesis in medulloblastoma
    Nat. Cancer Pub Date : 2020-08-18
    Apolinar Maya-Mendoza; Jiri Bartek

    Replication stress fuels chromosomal instability, tumor heterogeneity and therapy resistance. The Sonic hedgehog pathway is now linked to an unorthodox form of replication stress in cerebellar granular-cell progenitors through deregulated firing of DNA replication origins, with implications for the pathogenesis, genomic instability and treatment of medulloblastoma.

  • A brave new virtual conferencing world
    Nat. Cancer Pub Date : 2020-08-18

    Travel restrictions due to COVID-19 have forced the science world to change conference and networking practices. Retaining the positives of virtual interactions should be a priority in the post-pandemic era.

  • Applications of organoids for cancer biology and precision medicine
    Nat. Cancer Pub Date : 2020-08-18
    Yuan-Hung Lo; Kasper Karlsson; Calvin J. Kuo

    Organoid technologies enable the creation of in vitro physiologic systems that model tissues of origin more accurately than classical culture approaches. Seminal characteristics of these systems, including three-dimensional structure and recapitulation of self-renewal, differentiation and disease pathology, render organoids eminently suited as hybrids that combine the experimental tractability of traditional

  • Integrated analysis of patient samples identifies biomarkers for venetoclax efficacy and combination strategies in acute myeloid leukemia
    Nat. Cancer Pub Date : 2020-08-18
    Haijiao Zhang; Yusuke Nakauchi; Thomas Köhnke; Melissa Stafford; Daniel Bottomly; Rozario Thomas; Beth Wilmot; Shannon K. McWeeney; Ravindra Majeti; Jeffrey W. Tyner

    Deregulation of the BCL2 gene family plays an important role in the pathogenesis of acute myeloid leukemia (AML). A BCL2 inhibitor, venetoclax, has received approval from the US Food and Drug Administration for the treatment of AML. However, upfront and acquired drug resistance ensues, in part due to the clinical and genetic heterogeneity of AML, highlighting the importance of identifying biomarkers

  • Pseudovirus for immunotherapy
    Nat. Cancer Pub Date : 2020-08-10
    Oliver Kepp; Guido Kroemer

    Locally injected lipid nanoparticles that deliver RNA to elicit danger signals and simultaneously contain RNA that encodes a membrane-anchored version of the cytokine IL-12 can induce immunogenic cell death in tumors. This multipronged platform induces anticancer immune responses to the injected lesion as well as to distant tumors and hence produces an abscopal effect.

  • Multifunctional oncolytic nanoparticles deliver self-replicating IL-12 RNA to eliminate established tumors and prime systemic immunity
    Nat. Cancer Pub Date : 2020-08-10
    Yingzhong Li; Zhijun Su; Weiyu Zhao; Xinfu Zhang; Noor Momin; Chengxiang Zhang; K. Dane Wittrup; Yizhou Dong; Darrell J. Irvine; Ron Weiss

    Therapies that synergistically stimulate immunogenic cancer cell death (ICD), inflammation and immune priming are of great interest for cancer immunotherapy. However, even multi-agent therapies often fail to trigger all of the steps necessary for self-sustaining antitumor immunity. Here we describe self-replicating RNAs encapsulated in lipid nanoparticles (LNP), which combine three key elements: (1)

  • Discovery through clinical sequencing in oncology
    Nat. Cancer Pub Date : 2020-08-10
    Mark T. A. Donoghue; Alison M. Schram; David M. Hyman; Barry S. Taylor

    The molecular characterization of tumors now informs clinical cancer care for many patients. This advent of molecular oncology has been driven by the expanding number of therapeutic biomarkers that can predict sensitivity to both approved agents and investigational agents. Beyond its role in driving clinical-trial enrollments and guiding therapy in individual patients, large-scale clinical genomics

  • Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab
    Nat. Cancer Pub Date : 2020-08-03
    Scott V. Bratman; S. Y. Cindy Yang; Marco A. J. Iafolla; Zhihui Liu; Aaron R. Hansen; Philippe L. Bedard; Stephanie Lheureux; Anna Spreafico; Albiruni Abdul Razak; Svetlana Shchegrova; Maggie Louie; Paul Billings; Bernhard Zimmermann; Himanshu Sethi; Alexey Aleshin; Dax Torti; Kayla Marsh; Jenna Eagles; Iulia Cirlan; Youstina Hanna; Derek L. Clouthier; Scott C. Lien; Pamela S. Ohashi; Wei Xu; Lillian

    Immune checkpoint blockade (ICB) provides clinical benefit to a subset of patients with cancer. However, existing biomarkers do not reliably predict treatment response across diverse cancer types. Limited data exist to show how serial circulating tumor DNA (ctDNA) testing may perform as a predictive biomarker in patients receiving ICB. We conducted a prospective phase II clinical trial to assess ctDNA

  • SARS-CoV-2 infection in the Italian Veneto region: adverse outcomes in patients with cancer
    Nat. Cancer Pub Date : 2020-07-31
    Massimo Rugge; Manuel Zorzi; Stefano Guzzinati

    In 84,246 consecutive Italians tested for SARS-CoV-2, we examined the prevalence of cancer and clinical outcomes of viral infection. Overall, 5.7% (4,789/84,246) had previously been diagnosed with cancer and, among the SARS-CoV-2-positive (CV2+ve) patients, 7.8% had a cancer diagnosis (723/9,275). Prevalence of cancer was not associated with risk of infection (odds ratio of 0.97; 95% confidence interval

  • Deep learning links histology, molecular signatures and prognosis in cancer
    Nat. Cancer Pub Date : 2020-07-27
    Nicolas Coudray; Aristotelis Tsirigos

    Deep learning can be used to predict genomic alterations on the basis of morphological features learned from digital histopathology. Two independent pan-cancer studies now show that automated learning from digital pathology slides and genomics can potentially delineate broader classes of molecular signatures and prognostic associations across cancer types.

  • Pan-cancer image-based detection of clinically actionable genetic alterations
    Nat. Cancer Pub Date : 2020-07-27
    Jakob Nikolas Kather; Lara R. Heij; Heike I. Grabsch; Chiara Loeffler; Amelie Echle; Hannah Sophie Muti; Jeremias Krause; Jan M. Niehues; Kai A. J. Sommer; Peter Bankhead; Loes F. S. Kooreman; Jefree J. Schulte; Nicole A. Cipriani; Roman D. Buelow; Peter Boor; Nadina Ortiz-Brüchle; Andrew M. Hanby; Valerie Speirs; Sara Kochanny; Akash Patnaik; Andrew Srisuwananukorn; Hermann Brenner; Michael Hoffmeister;

    Molecular alterations in cancer can cause phenotypic changes in tumor cells and their microenvironment. Routine histopathology tissue slides, which are ubiquitously available, can reflect such morphological changes. Here, we show that deep learning can consistently infer a wide range of genetic mutations, molecular tumor subtypes, gene expression signatures and standard pathology biomarkers directly

  • Pan-cancer computational histopathology reveals mutations, tumor composition and prognosis
    Nat. Cancer Pub Date : 2020-07-27
    Yu Fu; Alexander W. Jung; Ramon Viñas Torne; Santiago Gonzalez; Harald Vöhringer; Artem Shmatko; Lucy R. Yates; Mercedes Jimenez-Linan; Luiza Moore; Moritz Gerstung

    We use deep transfer learning to quantify histopathological patterns across 17,355 hematoxylin and eosin-stained histopathology slide images from 28 cancer types and correlate these with matched genomic, transcriptomic and survival data. This approach accurately classifies cancer types and provides spatially resolved tumor and normal tissue distinction. Automatically learned computational histopathological

  • No borders in science
    Nat. Cancer Pub Date : 2020-07-21

    Government policies that threaten the international mobility of biomedical students, researchers and physicians stand to imperil scientific progress and innovation at a time when supporting them is paramount.

  • Sonic hedgehog accelerates DNA replication to cause replication stress promoting cancer initiation in medulloblastoma
    Nat. Cancer Pub Date : 2020-07-20
    Lukas Tamayo-Orrego; David Gallo; Frédéric Racicot; Amandine Bemmo; Sushmetha Mohan; Brandon Ho; Samer Salameh; Trang Hoang; Andrew P. Jackson; Grant W. Brown; Frédéric Charron

    The mechanisms generating cancer-initiating mutations are not well understood. Sonic hedgehog (SHH) pathway activation is frequent in medulloblastoma (MB), with PTCH1 mutations being a common initiating event. Here we investigated the role of the developmental mitogen SHH in initiating carcinogenesis in the cells of origin: granule cell progenitors (GCPs). We delineate a molecular mechanism for tumor

  • Publisher Correction: Zeb2 drives invasive and microbiota-dependent colon carcinoma
    Nat. Cancer Pub Date : 2020-07-10
    Karolina Slowicka; Ioanna Petta; Gillian Blancke; Esther Hoste; Emilie Dumas; Mozes Sze; Hanna Vikkula; Enrico Radaelli; Jody J. Haigh; Sven Jonckheere; Joachim Taminau; Niels Vandamme; Andy Wullaert; Eugene Tulchinsky; David Nittner; Pieter Van Vlierberghe; Gert De Hertogh; Pamela Baldin; Emre Etlioglu; Pratyaksha Wirapati; Louis Boon; Bart N. Lambrecht; Chris Callewaert; Sabine Tejpar; Steven Goossens;

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

  • The current paradigm and challenges ahead for the dormancy of disseminated tumor cells
    Nat. Cancer Pub Date : 2020-07-06
    Emma Risson; Ana Rita Nobre; Veronique Maguer-Satta; Julio A. Aguirre-Ghiso

    Disseminated tumor cells (DTCs) are known to enter a state of dormancy that is achieved via growth arrest of DTCs and/or a form of population equilibrium state, strongly influenced by the organ microenvironment. During this time, expansion of residual disseminated cancer is paused and DTCs survive to fuel relapse, sometimes decades later. This notion has opened a new window of opportunity for intervening

  • Aldolase B suppresses hepatocellular carcinogenesis by inhibiting G6PD and pentose phosphate pathways
    Nat. Cancer Pub Date : 2020-07-06
    Min Li; Xuxiao He; Weixing Guo; Hongming Yu; Shicheng Zhang; Ningning Wang; Guijun Liu; Rina Sa; Xia Shen; Yabo Jiang; Yufu Tang; Yujuan Zhuo; Chunzhao Yin; Qiaochu Tu; Nan Li; Xiaoqun Nie; Yu Li; Zhimin Hu; Hanwen Zhu; Jianping Ding; Zi Li; Te Liu; Fan Zhang; He Zhou; Shengxian Li; Jiang Yue; Zheng Yan; Shuqun Cheng; Yongzhen Tao; Huiyong Yin

    Metabolic reprogramming is a core hallmark of cancer but it remains poorly defined in hepatocellular carcinogenesis (HCC). Here we show that hepatic aldolase B (Aldob) suppresses HCC by directly binding and inhibiting the rate-limiting enzyme in the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PD). A stage-dependent decrease of Aldob and increase of G6PD in human tumors are correlated

  • The deubiquitinase USP25 supports colonic inflammation and bacterial infection and promotes colorectal cancer
    Nat. Cancer Pub Date : 2020-07-06
    Xiao-Meng Wang; Ci Yang; Yin Zhao; Zhi-Gao Xu; Wei Yang; Peng Wang; Dandan Lin; Bin Xiong; Jing-Yuan Fang; Chen Dong; Bo Zhong

    Bacterial infection or abnormal colonization in the gastrointestinal system is associated with subsets of inflammatory bowel disease and colorectal cancer. Here we demonstrated essential roles of ubiquitin-specific protease 25 (USP25) in experimental colitis, bacterial infections and colon cancer. Knockout or pharmacologic inhibition of USP25 potentiated immune responses after induction of experimental

  • Cancer-associated fibroblast compositions change with breast cancer progression linking the ratio of S100A4 + and PDPN + CAFs to clinical outcome
    Nat. Cancer Pub Date : 2020-06-29
    Gil Friedman; Oshrat Levi-Galibov; Eyal David; Chamutal Bornstein; Amir Giladi; Maya Dadiani; Avi Mayo; Coral Halperin; Meirav Pevsner-Fischer; Hagar Lavon; Shimrit Mayer; Reinat Nevo; Yaniv Stein; Nora Balint-Lahat; Iris Barshack; H. Raza Ali; Carlos Caldas; Einav Nili-Gal-Yam; Uri Alon; Ido Amit; Ruth Scherz-Shouval

    Tumors are supported by cancer-associated fibroblasts (CAFs). CAFs are heterogeneous and carry out distinct cancer-associated functions. Understanding the full repertoire of CAFs and their dynamic changes as tumors evolve could improve the precision of cancer treatment. Here we comprehensively analyze CAFs using index and transcriptional single-cell sorting at several time points along breast tumor

  • TNF-shaped microbiota promotes cancer
    Nat. Cancer Pub Date : 2020-06-22
    Giorgio Trinchieri

    The approval of anti-TNF therapy for colitis over 20 years ago represented a paradigm shift for the treatment of this disease. Anti-TNF therapy is now shown to prevent colitis-associated colon cancer in mice by modifying the gut microbiota composition and transcriptional activity, including genes in Escherichia coli that control colibactin synthesis.

  • Amending microbiota by targeting intestinal inflammation with TNF blockade attenuates development of colorectal cancer
    Nat. Cancer Pub Date : 2020-06-22
    Ye Yang; Raad Z. Gharaibeh; Rachel C. Newsome; Christian Jobin

    Intestinal inflammation and microbiota are two important components of colorectal cancer (CRC) etiology. However, it is not clear how tuning inflammation using clinically relevant anti-inflammatory treatment impacts microbiota or whether this consequently influences CRC outcome. Here, using chemically induced (DSS/Apcmin/+) and spontaneous (Apcmin/+;Il10−/−) mouse CRC models colonized by colibactin-producing

  • Mapping the switch that drives the pre-metastatic niche
    Nat. Cancer Pub Date : 2020-06-22
    Sabina Kaczanowska; Rosandra N. Kaplan

    The pre-metastatic niche is a complex microenvironment formed by the influence of tumor-derived factors on stromal and immune cells at distant sites of disseminated tumor-cell colonization. Signaling through the kinase p38α and regulation of the type I interferon receptor are now linked to formation of the pre-metastatic niche.

  • PD-L1 expression by dendritic cells is a key regulator of T-cell immunity in cancer
    Nat. Cancer Pub Date : 2020-06-22
    Soyoung A. Oh; Dai-Chen Wu; Jeanne Cheung; Armando Navarro; Huizhong Xiong; Rafael Cubas; Klara Totpal; Henry Chiu; Yan Wu; Laetitia Comps-Agrar; Andrew M. Leader; Miriam Merad; Merone Roose-Germa; Soren Warming; Minhong Yan; Jeong M. Kim; Sascha Rutz; Ira Mellman

    Inhibiting the programmed death-1 (PD-1) pathway is one of the most effective approaches to cancer immunotherapy, but its mechanistic basis remains incompletely understood. Binding of PD-1 to its ligand PD-L1 suppresses T-cell function in part by inhibiting CD28 signaling. Tumor cells and infiltrating myeloid cells can express PD-L1, with myeloid cells being of particular interest as they also express

  • Delineating the evolutionary dynamics of cancer from theory to reality
    Nat. Cancer Pub Date : 2020-06-22
    Ivana Bozic; Catherine J. Wu

    Uncovering and quantifying the laws of the evolutionary dynamics of cancer, in particular in the context of specific genetic lesions and in individual patients, has the potential to revolutionize precision oncology. Recent technological advances in the study of human cancer have increased access to in vivo human data and have thereby facilitated the confirmation or refutation of existing theoretical

  • The serine hydroxymethyltransferase-2 (SHMT2) initiates lymphoma development through epigenetic tumor suppressor silencing
    Nat. Cancer Pub Date : 2020-06-22
    Sara Parsa; Ana Ortega-Molina; Hsia-Yuan Ying; Man Jiang; Matt Teater; Jiahui Wang; Chunying Zhao; Ed Reznik; Joyce P. Pasion; David Kuo; Prathibha Mohan; Shenqiu Wang; Jeannie M. Camarillo; Paul M. Thomas; Neeraj Jain; Javier Garcia-Bermudez; Byoung-kyu Cho; Wayne Tam; Neil L. Kelleher; Nicholas Socci; Ahmet Dogan; Elisa De Stanchina; Giovanni Ciriello; Michael R. Green; Sheng Li; Kivanc Birsoy; Ari

    Cancer cells adapt their metabolic activities to support growth and proliferation. However, increased activity of metabolic enzymes is not usually considered an initiating event in the malignant process. Here, we investigate the possible role of the enzyme serine hydroxymethyltransferase-2 (SHMT2) in lymphoma initiation. SHMT2 localizes to the most frequent region of copy number gains at chromosome

  • Multi-omic analysis reveals significantly mutated genes and DDX3X as a sex-specific tumor suppressor in cutaneous melanoma
    Nat. Cancer Pub Date : 2020-06-22
    Rached Alkallas; Mathieu Lajoie; Dan Moldoveanu; Karen Vo Hoang; Philippe Lefrançois; Marine Lingrand; Mozhdeh Ahanfeshar-Adams; Kevin Watters; Alan Spatz; Jonathan H. Zippin; Hamed S. Najafabadi; Ian R. Watson

    The high background tumor mutation burden in cutaneous melanoma limits the ability to identify significantly mutated genes (SMGs) that drive this cancer. To address this, we performed a mutation significance study of over 1,000 melanoma exomes, combined with a multi-omic analysis of 470 cases from The Cancer Genome Atlas. We discovered several SMGs with co-occurring loss-of-heterozygosity and loss-of-function

  • Publisher Correction: Long-distance modulation of bystander tumor cells by CD8 + T-cell-secreted IFN-γ
    Nat. Cancer Pub Date : 2020-06-17
    Mirjam E. Hoekstra; Laura Bornes; Feline E. Dijkgraaf; Daisy Philips; Iris N. Pardieck; Mireille Toebes; Daniela S. Thommen; Jacco van Rheenen; Ton N. M. Schumacher

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

  • Author Correction: A practical framework and online tool for mutational signature analyses show intertissue variation and driver dependencies
    Nat. Cancer Pub Date : 2020-06-17
    Andrea Degasperi; Tauanne Dias Amarante; Jan Czarnecki; Scott Shooter; Xueqing Zou; Dominik Glodzik; Sandro Morganella; Arjun S. Nanda; Cherif Badja; Gene Koh; Sophie E. Momen; Ilias Georgakopoulos-Soares; João M. L. Dias; Jamie Young; Yasin Memari; Helen Davies; Serena Nik-Zainal

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

  • Speaking up against inequity and racism
    Nat. Cancer Pub Date : 2020-06-16

    Inequalities are prevalent across the spectrum of cancer research and patient care, with destructive repercussions for people and society. We cannot ignore them and must act against the social injustices that perpetuate them.

  • Zeb2 drives invasive and microbiota-dependent colon carcinoma
    Nat. Cancer Pub Date : 2020-06-15
    Karolina Slowicka; Ioanna Petta; Gillian Blancke; Esther Hoste; Emilie Dumas; Mozes Sze; Hanna Vikkula; Enrico Radaelli; Jody J. Haigh; Sven Jonckheere; Joachim Taminau; Niels Vandamme; Andy Wullaert; Eugene Tulchinsky; David Nittner; Pieter Van Vlierberghe; Gert De Hertogh; Pamela Baldin; Emre Etlioglu; Pratyaksha Wirapati; Louis Boon; Bart N. Lambrecht; Chris Callewaert; Sabine Tejpar; Steven Goossens;

    Colorectal cancer (CRC) is highly prevalent in Western society, and increasing evidence indicates strong contributions of environmental factors and the intestinal microbiota to CRC initiation, progression and even metastasis. We have identified a synergistic inflammatory tumor-promoting mechanism through which the resident intestinal microbiota boosts invasive CRC development in an epithelial-to-mesenchymal

  • Keap1ing an eye on Slc33A1
    Nat. Cancer Pub Date : 2020-06-08
    Luke A. Gilbert

    KEAP1 is a tumor suppressor encoded by a gene commonly mutated in lung cancer. A systematic search for Keap1-mutant cancer vulnerabilities now reveals that Slc33a1 is a context-specific essential gene that represents a promising new anti-cancer target.

  • Keap1 mutation renders lung adenocarcinomas dependent on Slc33a1
    Nat. Cancer Pub Date : 2020-06-08
    Rodrigo Romero; Francisco J. Sánchez-Rivera; Peter M. K. Westcott; Kim L. Mercer; Arjun Bhutkar; Alexander Muir; Tania J. González Robles; Swanny Lamboy Rodríguez; Laura Z. Liao; Sheng Rong Ng; Leanne Li; Caterina I. Colón; Santiago Naranjo; Mary Clare Beytagh; Caroline A. Lewis; Peggy P. Hsu; Roderick T. Bronson; Matthew G. Vander Heiden; Tyler Jacks

    Approximately 20–30% of human lung adenocarcinomas (LUADs) harbor mutations in Kelch-like ECH-associated protein 1 (KEAP1) that hyperactivate the nuclear factor, erythroid 2-like 2 (NFE2L2) antioxidant program. We previously showed that Kras-driven Keap1-mutant LUAD is highly aggressive and dependent on glutaminolysis. Here we performed a druggable genome CRISPR screen and uncovered a Keap1-mutant-specific

  • Immunoediting of cancer metastasis by NK cells
    Nat. Cancer Pub Date : 2020-06-01
    Kyohei Nakamura; Mark J. Smyth

    Natural killer (NK) cells serve a critical role in the control of metastasis. NK cells are now shown to preferentially control monoclonal metastases derived from single circulating tumor cells rather than polyclonal metastases derived from cell clusters. These findings provide further evidence that NK cells are linked to metastatic cell immunoediting.

  • Resistance to natural killer cell immunosurveillance confers a selective advantage to polyclonal metastasis
    Nat. Cancer Pub Date : 2020-06-01
    Hin Ching Lo; Zhan Xu; Ik Sun Kim; Bradley Pingel; Sergio Aguirre; Srikanth Kodali; Jun Liu; Weijie Zhang; Aaron M. Muscarella; Sarah M. Hein; Alexander S. Krupnick; Joel R. Neilson; Silke Paust; Jeffrey M. Rosen; Hai Wang; Xiang H.-F. Zhang

    Polyclonal metastases frequently arise from clusters of circulating tumor cells (CTCs). CTC clusters metastasize better than single CTCs, but the underlying molecular mechanisms are poorly understood. Here, we show that polyclonal metastatic seeds exhibit higher resistance to natural killer (NK) cell killing. Using breast cancer models, we observed higher proportions of polyclonal lung metastasis in

  • Rethinking cancer clinical trials for COVID-19 and beyond
    Nat. Cancer Pub Date : 2020-05-29
    Gary J. Doherty; Mehmet Goksu; Bruno H. R. de Paula

    The risks posed to patients with cancer by the current COVID-19 pandemic demand rapid structural changes in healthcare delivery, with many positive changes likely to continue long term. An immediate critical reassessment of trial methodology based on clinical and scientific priorities is essential to ensure the resilience of clinical cancer research and optimize patient-centered care.

  • Activation of p38α stress-activated protein kinase drives the formation of the pre-metastatic niche in the lungs
    Nat. Cancer Pub Date : 2020-05-25
    Jun Gui; Farima Zahedi; Angelica Ortiz; Christina Cho; Kanstantsin V. Katlinski; Kevin Alicea-Torres; Jinyang Li; Leslie Todd; Hongru Zhang; Daniel P. Beiting; Cindy Sander; John M. Kirkwood; Bryan E. Snow; Andrew C. Wakeham; Tak W. Mak; J. Alan Diehl; Constantinos Koumenis; Sandra W. Ryeom; Ben Z. Stanger; Ellen Puré; Dmitry I. Gabrilovich; Serge Y. Fuchs

    Primary tumor-derived factors act upon normal cells to generate a pre-metastatic niche, which promotes colonization of target organs by disseminated malignant cells. Here we report that tumor-derived factor-induced activation of the p38α kinase in lung fibroblasts plays a critical role in the formation of a pre-metastatic niche in the lungs and subsequent pulmonary metastases. Activation of p38α led

  • Genomics-guided pre-clinical development of cancer therapies
    Nat. Cancer Pub Date : 2020-05-22
    Hayley E. Francies; Ultan McDermott; Mathew J. Garnett

    Since the approval of trastuzumab for the treatment of breast cancers more than two decades ago, many clinically effective targeted anti-cancer therapies have been developed. Here we consider the evidence that supports genomics-guided drug development and review the concept of oncogene addiction, including recent findings that inform this therapeutic approach. We consider non-oncogene addiction and

  • The T cell differentiation landscape is shaped by tumour mutations in lung cancer.
    Nat. Cancer Pub Date : 2020-05-22
    Ehsan Ghorani,James L Reading,Jake Y Henry,Marc Robert de Massy,Rachel Rosenthal,Virginia Turati,Kroopa Joshi,Andrew J S Furness,Assma Ben Aissa,Sunil Kumar Saini,Sofie Ramskov,Andrew Georgiou,Mariana Werner Sunderland,Yien Ning Sophia Wong,Maria Vila De Mucha,William Day,Felipe Galvez-Cancino,Pablo D Becker,Imran Uddin,Mazlina Ismail,Tahel Ronel,Annemarie Woolston,Mariam Jamal-Hanjani,Selvaraju Veeriah

    Tumour mutational burden (TMB) predicts immunotherapy outcome in non-small cell lung cancer (NSCLC), consistent with immune recognition of tumour neoantigens. However, persistent antigen exposure is detrimental for T cell function. How TMB affects CD4 and CD8 T cell differentiation in untreated tumours and whether this affects patient outcomes is unknown. Here, we paired high-dimensional flow cytometry

  • The impact of the COVID-19 pandemic on cancer care.
    Nat. Cancer Pub Date : 2020-05-20
    Mike Richards,Michael Anderson,Paul Carter,Benjamin L Ebert,Elias Mossialos

    The COVID-19 pandemic has disrupted the spectrum of cancer care, including delaying diagnoses and treatment and halting clinical trials. In response, healthcare systems are rapidly reorganizing cancer services to ensure that patients continue to receive essential care while minimizing exposure to SARS-CoV-2 infection.

  • Rel-ating myeloid cells to cancer therapy
    Nat. Cancer Pub Date : 2020-05-18
    Hideyuki Takahashi; Judy Varner

    Immune-checkpoint blockade holds great promise in cancer therapy; however, T cell–specific checkpoint inhibitors are not effective for all patients with cancer. The transcription factor c-Rel is now shown to regulate pro-inflammatory polarization of myeloid cells and modulate anti-tumor immune responses.

  • c-Rel is a myeloid checkpoint for cancer immunotherapy
    Nat. Cancer Pub Date : 2020-05-18
    Ting Li; Xinyuan Li; Ali Zamani; Wei Wang; Chin-Nien Lee; Mingyue Li; George Luo; Emily Eiler; Honghong Sun; Sankar Ghosh; Jian Jin; Ramachandran Murali; Qingguo Ruan; Weiyun Shi; Youhai H. Chen

    Immunotherapy that targets lymphoid cell checkpoints holds great promise for curing cancer. However, many cancer patients do not respond to this form of therapy. In addition to lymphoid cells, myeloid cells play essential roles in controlling immunity to cancer. Whether myeloid checkpoints exist that can be targeted to treat cancer is not well established. Here we show that c-Rel, a member of the nuclear

  • The tightrope of science, media and politics.
    Nat. Cancer Pub Date : 2020-05-14

    The urgent need to address COVID-19 has highlighted the delicate relationships among science, politics and the media. To achieve a successful long-term response to the pandemic, stakeholders need to be guided by data, integrity and a sense of responsibility toward the public.

  • Age-correlated protein and transcript expression in breast cancer and normal breast tissues is dominated by host endocrine effects
    Nat. Cancer Pub Date : 2020-05-11
    Tomo Osako; Hakwoo Lee; Gulisa Turashvili; Derek Chiu; Steven McKinney; Stacey E. P. Joosten; Darcy Wilkinson; Torsten O. Nielsen; Wilbert Zwart; Joanne T. Emerman; Connie J. Eaves; Carlos Caldas; Samuel Aparicio

    The magnitude and scope of intrinsic age-correlated and host endocrine age-correlated gene expression in breast cancer is not well understood. From age-correlated gene expression in 3,071 breast cancer transcriptomes and epithelial protein expression of 42 markers in 5,001 breast cancers and 537 normal breast tissues, we identified a majority of age-correlated genes as putatively regulated by age-dependent

  • Stepwise immune alterations in multiple myeloma progression
    Nat. Cancer Pub Date : 2020-04-28
    Qiming Zhang; Zemin Zhang

    Studies of the tumor microenvironment have provided fundamental insights into cancer progression. A new study now delineates the dynamics of immune-cell alterations at the single-cell level and across stages of multiple myeloma, elucidating the microenvironmental changes involved in the precursor states of the disease.

  • Single-cell RNA sequencing reveals compromised immune microenvironment in precursor stages of multiple myeloma
    Nat. Cancer Pub Date : 2020-04-27
    Oksana Zavidij; Nicholas J. Haradhvala; Tarek H. Mouhieddine; Romanos Sklavenitis-Pistofidis; Songjie Cai; Mairead Reidy; Mahshid Rahmat; Abdallah Flaifel; Benjamin Ferland; Nang K. Su; Michael P. Agius; Jihye Park; Salomon Manier; Mark Bustoros; Daisy Huynh; Marzia Capelletti; Brianna Berrios; Chia-Jen Liu; Meng Xiao He; Esteban Braggio; Rafael Fonseca; Yosef E. Maruvka; Jennifer L. Guerriero; Melissa

    Precursor states of multiple myeloma (MM) and its native tumor microenvironment need in-depth molecular characterization to better stratify and treat patients at risk. Using single-cell RNA sequencing of bone marrow cells from precursor stages, monoclonal gammopathy of unknown significance and smoldering MM, to full-blown MM alongside healthy donors, we demonstrate early immune changes during patient

  • Crowdsourcing a crisis response for COVID-19 in oncology.
    Nat. Cancer Pub Date : 2020-04-21
    Aakash Desai,Jeremy Warner,Nicole Kuderer,Mike Thompson,Corrie Painter,Gary Lyman,Gilberto Lopes

    Crowdsourcing efforts are currently underway to collect and analyze data from patients with cancer who are affected by the COVID-19 pandemic. These community-led initiatives will fill key knowledge gaps to tackle crucial clinical questions on the complexities of infection with the causative coronavirus SARS-Cov-2 in the large, heterogeneous group of vulnerable patients with cancer.

  • eIF5B drives integrated stress response-dependent translation of PD-L1 in lung cancer
    Nat. Cancer Pub Date : 2020-04-20
    Shruthy Suresh; BeiBei Chen; Jingfei Zhu; Ryan J. Golden; Changzheng Lu; Bret M. Evers; Nicole Novaresi; Bethany Smith; Xiaowei Zhan; Vanessa Schmid; Sojeong Jun; Chelsea M. Karacz; Michael Peyton; Lin Zhong; Zhuoyu Wen; Adwait Amod Sathe; Chao Xing; Carmen Behrens; Ignacio I. Wistuba; Guanghua Xiao; Yang Xie; Yang-Xin Fu; John D. Minna; Joshua T. Mendell; Kathryn A. O’Donnell
  • An in vivo genome-wide CRISPR screen identifies the RNA-binding protein Staufen2 as a key regulator of myeloid leukemia
    Nat. Cancer Pub Date : 2020-04-20
    Jeevisha Bajaj; Michael Hamilton; Yutaka Shima; Kendall Chambers; Kyle Spinler; Eric L. Van Nostrand; Brian A. Yee; Steven M. Blue; Michael Chen; David Rizzeri; Charles Chuah; Vivian G. Oehler; H. Elizabeth Broome; Roman Sasik; James Scott-Browne; Anjana Rao; Gene W. Yeo; Tannishtha Reya
  • Microbiome genomics for cancer prediction
    Nat. Cancer Pub Date : 2020-04-20
    Lorenz Adlung; Eran Elinav; Tim F. Greten; Firouzeh Korangy
  • The genomic landscape of advanced cancer
    Nat. Cancer Pub Date : 2020-04-13
    Esther Rheinbay
  • Pan-cancer analysis of advanced patient tumors reveals interactions between therapy and genomic landscapes
    Nat. Cancer Pub Date : 2020-04-13
    Erin Pleasance; Emma Titmuss; Laura Williamson; Harwood Kwan; Luka Culibrk; Eric Y. Zhao; Katherine Dixon; Kevin Fan; Reanne Bowlby; Martin R. Jones; Yaoqing Shen; Jasleen K. Grewal; Jahanshah Ashkani; Kathleen Wee; Cameron J. Grisdale; My Linh Thibodeau; Zoltan Bozoky; Hillary Pearson; Elisa Majounie; Tariq Vira; Reva Shenwai; Karen L. Mungall; Eric Chuah; Anna Davies; Mya Warren; Caralyn Reisle;
  • A biobank of small cell lung cancer CDX models elucidates inter- and intratumoral phenotypic heterogeneity
    Nat. Cancer Pub Date : 2020-04-13
    Kathryn L. Simpson; Ruth Stoney; Kristopher K. Frese; Nicole Simms; William Rowe; Simon P. Pearce; Sam Humphrey; Laura Booth; Derrick Morgan; Marek Dynowski; Francesca Trapani; Alessia Catozzi; Mitchell Revill; Thomas Helps; Melanie Galvin; Luc Girard; Daisuke Nonaka; Louise Carter; Matthew G. Krebs; Natalie Cook; Mathew Carter; Lynsey Priest; Alastair Kerr; Adi F. Gazdar; Fiona Blackhall; Caroline
  • 更新日期:2020-04-24
  • On being human in the face of a pandemic
    Nat. Cancer Pub Date : 2020-04-09

    As the COVID-19 pandemic sweeps through the world, we must reassess the principles that guide our individual and collective responses and the way we operate in society. In the face of crisis, we must lead with science and humanity.

Contents have been reproduced by permission of the publishers.
ACS ES&T Engineering
ACS ES&T Water