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  • Rise of the preprints
    Nat. Cancer Pub Date : 2020-11-17

    Nature Cancer encourages preprint sharing as a valuable means of research dissemination and scholarly communication.

    更新日期:2020-11-17
  • A nano-engager for iNKT cells in cancer
    Nat. Cancer Pub Date : 2020-11-17
    Mark A. Exley; Thomas Gensollen; Richard S. Blumberg

    Invariant natural killer T cells (iNKT cells) are innate-like CD1d-restricted T cells that have NK cell–like properties and bear an invariant T cell receptor (iTCR). iNKT cells have shown potential for cancer immunotherapy. A study now shows that stabilization of the iTCR–CD1d complex via a single-chain bi-specific antibody stimulates iNKT cell–mediated anti-tumor immunity.

    更新日期:2020-11-17
  • Future directions in preclinical and translational cancer neuroscience research
    Nat. Cancer Pub Date : 2020-11-17
    Ihsan Ekin Demir; Carmen Mota Reyes; Wasfi Alrawashdeh; Güralp O. Ceyhan; Sylvie Deborde; Helmut Friess; Kıvanç Görgülü; Rouzanna Istvanffy; David Jungwirth; Rohini Kuner; Maria Maryanovich; Shorook Na’ara; Simon Renders; Jami L. Saloman; Nicole N. Scheff; Hendrik Steenfadt; Pavel Stupakov; Vera Thiel; Divij Verma; Bengi Su Yilmaz; Ruth A. White; Timothy C. Wang; Richard J. Wong; Paul S. Frenette;

    Recent advances in cancer neuroscience necessitate the systematic analysis of neural influences in cancer as potential therapeutic targets in oncology. Here we outline recommendations for future preclinical and translational research in this field.

    更新日期:2020-11-17
  • A LIBRETTO to orchestrate targeted therapy
    Nat. Cancer Pub Date : 2020-11-17
    Melina E. Marmarelis; Roberto Chiarle; Chiara Ambrogio; Charu Aggarwal

    Although RET alterations are relatively frequent across tumor types, specific targeting of RET in the clinic has been challenging. Ambrogio, Aggarwal and colleagues provide their views on how mechanistic studies have swiftly translated into powerful targeted therapies in two recent clinical studies that led to the FDA approval of selpercatinib for certain tumors in which RET is altered.

    更新日期:2020-11-17
  • Accelerating precision medicine in metastatic prostate cancer
    Nat. Cancer Pub Date : 2020-11-17
    Joaquin Mateo; Rana McKay; Wassim Abida; Rahul Aggarwal; Joshi Alumkal; Ajjai Alva; Felix Feng; Xin Gao; Julie Graff; Maha Hussain; Fatima Karzai; Bruce Montgomery; William Oh; Vaibhav Patel; Dana Rathkopf; Matthew Rettig; Nikolaus Schultz; Matthew Smith; David Solit; Cora Sternberg; Eliezer Van Allen; David VanderWeele; Jake Vinson; Howard R. Soule; Arul Chinnaiyan; Eric Small; Jonathan W. Simons;

    Despite advances in the screening and treatment of prostate cancer, the therapy options available, particularly for later stages of the disease, remain limited, and the treatment-resistant setting represents a serious unmet medical need. Moreover, disease heterogeneity and disparities in patient access to medical advances result in considerable variability in outcomes across patients. Disease classification

    更新日期:2020-11-17
  • Mutational landscape influences immunotherapy outcomes among patients with non-small-cell lung cancer with human leukocyte antigen supertype B44
    Nat. Cancer Pub Date : 2020-11-16
    Amy L. Cummings; Jaklin Gukasyan; Henry Y. Lu; Tristan Grogan; Gemalene Sunga; Charlene M. Fares; Nicholas Hornstein; Jesse Zaretsky; James Carroll; Benjamin Bachrach; Wisdom O. Akingbemi; Debory Li; Zorawar Noor; Aaron Lisberg; Jonathan W. Goldman; David Elashoff; Alex A. T. Bui; Antoni Ribas; Steven M. Dubinett; Maura Rossetti; Edward B. Garon

    Human leukocyte antigen (HLA)-B has been recognized as a major determinant of discrepancies in disease outcomes, and recent evidence indicates a role in immune checkpoint blockade (ICB) efficacy. The B44 supertype, which features an electropositive binding pocket that preferentially displays peptides with negatively charged amino acid anchors, is associated with improved survival in ICB-treated melanoma

    更新日期:2020-11-16
  • Flt3 ligand augments immune responses to anti-DEC-205-NY-ESO-1 vaccine through expansion of dendritic cell subsets
    Nat. Cancer Pub Date : 2020-11-16
    Nina Bhardwaj; Philip A. Friedlander; Anna C. Pavlick; Marc S. Ernstoff; Brian R. Gastman; Brent A. Hanks; Brendan D. Curti; Mark R. Albertini; Jason J. Luke; Ana B. Blazquez; Sreekumar Balan; Davide Bedognetti; Joseph M. Beechem; Andrea S. Crocker; Leonard D’Amico; Patrick Danaher; Thomas A. Davis; Thomas Hawthorne; Bruce W. Hess; Tibor Keler; Lisa Lundgren; Chihiro Morishima; Nirasha Ramchurren;

    Generating responses to tumor antigens poses a challenge for immunotherapy. This phase II trial (NCT02129075) tested fms-like tyrosine kinase 3 (Flt3) ligand pre-treatment enhancement of responses to dendritic cell (DC)-targeting vaccines. We evaluated a regimen of Flt3L (CDX-301) to increase DCs and other antigen-presenting cells, poly-ICLC (TLR3 agonist that activates DCs) and a vaccine comprising

    更新日期:2020-11-16
  • Mutations in BRCA1 and BRCA2 differentially affect the tumor microenvironment and response to checkpoint blockade immunotherapy
    Nat. Cancer Pub Date : 2020-11-16
    Robert M. Samstein; Chirag Krishna; Xiaoxiao Ma; Xin Pei; Ken-Wing Lee; Vladimir Makarov; Fengshen Kuo; Jonathan Chung; Raghvendra M. Srivastava; Tanaya A. Purohit; Douglas R. Hoen; Rajarsi Mandal; Jeremy Setton; Wei Wu; Rachna Shah; Besnik Qeriqi; Qing Chang; Sviatoslav Kendall; Lior Braunstein; Britta Weigelt; Pedro Blecua Carrillo Albornoz; Luc G. T. Morris; Diana L. Mandelker; Jorge S. Reis-Filho;

    Immune checkpoint blockade (ICB) has improved outcomes for patients with advanced cancer, but the determinants of response remain poorly understood. Here we report differential effects of mutations in the homologous recombination genes BRCA1 and BRCA2 on response to ICB in mouse and human tumors, and further show that truncating mutations in BRCA2 are associated with superior response compared to those

    更新日期:2020-11-16
  • CDK4/6 inhibition reprograms the breast cancer enhancer landscape by stimulating AP-1 transcriptional activity
    Nat. Cancer Pub Date : 2020-11-09
    April C. Watt; Paloma Cejas; Molly J. DeCristo; Otto Metzger-Filho; Enid Y. N. Lam; Xintao Qiu; Haley BrinJones; Nikolas Kesten; Rhiannon Coulson; Alba Font-Tello; Klothilda Lim; Raga Vadhi; Veerle W. Daniels; Joan Montero; Len Taing; Clifford A. Meyer; Omer Gilan; Charles C. Bell; Keegan D. Korthauer; Claudia Giambartolomei; Bogdan Pasaniuc; Ji-Heui Seo; Matthew L. Freedman; Cynthia Ma; Matthew J

    Pharmacologic inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) were designed to induce cancer cell cycle arrest. Recent studies have suggested that these agents also exert other effects, influencing cancer cell immunogenicity, apoptotic responses and differentiation. Using cell-based and mouse models of breast cancer together with clinical specimens, we show that CDK4/6 inhibitors induce remodeling

    更新日期:2020-11-12
  • CD25-T reg -depleting antibodies preserving IL-2 signaling on effector T cells enhance effector activation and antitumor immunity
    Nat. Cancer Pub Date : 2020-11-09
    Isabelle Solomon; Maria Amann; Anne Goubier; Frederick Arce Vargas; Dimitrios Zervas; Chen Qing; Jake Y. Henry; Ehsan Ghorani; Ayse U. Akarca; Teresa Marafioti; Anna Śledzińska; Mariana Werner Sunderland; Dafne Franz Demane; Joanne Ruth Clancy; Andrew Georgiou; Josephine Salimu; Pascal Merchiers; Mark Adrian Brown; Reto Flury; Jan Eckmann; Claudio Murgia; Johannes Sam; Bjoern Jacobsen; Estelle Marrer-Berger;

    Intratumoral regulatory T (Treg) cell abundance associates with diminished antitumor immunity and poor prognosis in human cancers. Recent work demonstrates that CD25, the high-affinity receptor subunit for interleukin (IL)-2, is a selective target for Treg depletion in mouse and human malignancies; however, anti-human CD25 antibodies have failed to deliver clinical responses against solid tumors due

    更新日期:2020-11-12
  • Author Correction: Pan-cancer image-based detection of clinically actionable genetic alterations
    Nat. Cancer Pub Date : 2020-11-03
    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;

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

    更新日期:2020-11-03
  • A ticking clock for B cell tumors
    Nat. Cancer Pub Date : 2020-11-02
    Paolo Strati; Michael R. Green

    Tumor-specific changes in DNA methylation are both acquired actively through transcription-coupled processes and passively accumulated over time. Analysis across B cell malignancies now shows that these changes provide insight into the cellular origin as well as the proliferative history of tumors and thereby have diagnostic value and prognostic value, respectively.

    更新日期:2020-11-02
  • The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome
    Nat. Cancer Pub Date : 2020-11-02
    Martí Duran-Ferrer; Guillem Clot; Ferran Nadeu; Renée Beekman; Tycho Baumann; Jessica Nordlund; Yanara Marincevic-Zuniga; Gudmar Lönnerholm; Alfredo Rivas-Delgado; Silvia Martín; Raquel Ordoñez; Giancarlo Castellano; Marta Kulis; Ana C. Queirós; Seung-Tae Lee; Joseph Wiemels; Romina Royo; Montserrat Puiggrós; Junyan Lu; Eva Giné; Sílvia Beà; Pedro Jares; Xabier Agirre; Felipe Prosper; Carlos López-Otín;

    We report a systematic analysis of the DNA methylation variability in 1,595 samples of normal cell subpopulations and 14 tumor subtypes spanning the entire human B-cell lineage. Differential methylation among tumor entities relates to differences in cellular origin and to de novo epigenetic alterations, which allowed us to build an accurate machine learning-based diagnostic algorithm. We identify extensive

    更新日期:2020-11-02
  • Mutant Kras co-opts a proto-oncogenic enhancer network in inflammation-induced metaplastic progenitor cells to initiate pancreatic cancer
    Nat. Cancer Pub Date : 2020-11-02
    Yong Li; Yi He; Junya Peng; Zhendong Su; Zeyao Li; Bingjie Zhang; Jing Ma; Meilian Zhuo; Di Zou; Xinde Liu; Xinhong Liu; Wenze Wang; Dan Huang; Mengyue Xu; Jianbin Wang; Haiteng Deng; Jing Xue; Wei Xie; Xun Lan; Mo Chen; Yupei Zhao; Wenming Wu; Charles J. David

    Kras-activating mutations display the highest incidence in pancreatic ductal adenocarcinoma. Pancreatic inflammation accelerates mutant Kras-driven tumorigenesis in mice, suggesting high selectivity in the cells that oncogenic Kras transforms, although the mechanisms dictating this specificity are poorly understood. Here we show that pancreatic inflammation is coupled to the emergence of a transient

    更新日期:2020-11-02
  • Multimodal mapping of the tumor and peripheral blood immune landscape in human pancreatic cancer
    Nat. Cancer Pub Date : 2020-10-26
    Nina G. Steele; Eileen S. Carpenter; Samantha B. Kemp; Veerin R. Sirihorachai; Stephanie The; Lawrence Delrosario; Jenny Lazarus; El-ad David Amir; Valerie Gunchick; Carlos Espinoza; Samantha Bell; Lindsey Harris; Fatima Lima; Valerie Irizarry-Negron; Daniel Paglia; Justin Macchia; Angel Ka Yan Chu; Heather Schofield; Erik-Jan Wamsteker; Richard Kwon; Allison Schulman; Anoop Prabhu; Ryan Law; Arjun

    Pancreatic ductal adenocarcinoma (PDA) is characterized by an immune-suppressive tumor microenvironment that renders it largely refractory to immunotherapy. We implemented a multimodal analysis approach to elucidate the immune landscape in PDA. Using a combination of CyTOF, single-cell RNA sequencing and multiplex immunohistochemistry on patient tumors, matched blood and non-malignant samples, we uncovered

    更新日期:2020-10-28
  • Fatty acid metabolism underlies venetoclax resistance in acute myeloid leukemia stem cells
    Nat. Cancer Pub Date : 2020-10-26
    Brett M. Stevens; Courtney L. Jones; Daniel A. Pollyea; Rachel Culp-Hill; Angelo D’Alessandro; Amanda Winters; Anna Krug; Diana Abbott; Madeline Goosman; Shanshan Pei; Haobin Ye; Austin E. Gillen; Michael W. Becker; Michael R. Savona; Clayton Smith; Craig T. Jordan

    Venetoclax with azacitidine (ven/aza) has emerged as a promising treatment regimen for acute myeloid leukemia (AML), with a high percentage of clinical remissions in newly diagnosed patients. However, approximately 30% of newly diagnosed patients and the majority of patients who have relapsed do not achieve remission with ven/aza. We previously reported that ven/aza efficacy is based on eradication

    更新日期:2020-10-28
  • mtDNA mutations help support cancer cells
    Nat. Cancer Pub Date : 2020-10-19
    Hiran A. Prag; Michael P. Murphy

    Mitochondrial DNA damage, metabolic disruption and aging have all been associated with cancer. These three threads are now woven together to show that aging-associated somatic mutations to mitochondrial DNA alter mitochondrial serine metabolism to support cell transformation and colon-cancer development.

    更新日期:2020-10-19
  • Mutational and functional genetics mapping of chemotherapy resistance mechanisms in relapsed acute lymphoblastic leukemia
    Nat. Cancer Pub Date : 2020-10-19
    Koichi Oshima; Junfei Zhao; Pablo Pérez-Durán; Jessie A. Brown; Juan Angel Patiño-Galindo; Timothy Chu; Aidan Quinn; Thomas Gunning; Laura Belver; Alberto Ambesi-Impiombato; Valeria Tosello; Zhengqiang Wang; Maria Luisa Sulis; Motohiro Kato; Katsuyoshi Koh; Maddalena Paganin; Giuseppe Basso; Milagros Balbin; Concepcion Nicolas; Julie M. Gastier-Foster; Meenakshi Devidas; Mignon L. Loh; Elisabeth Paietta;

    Multiagent combination chemotherapy can be curative in acute lymphoblastic leukemia (ALL). Still, patients with primary refractory disease or with relapsed leukemia have a very poor prognosis. Here we integrate an in-depth dissection of the mutational landscape across diagnostic and relapsed pediatric and adult ALL samples with genome-wide CRISPR screen analysis of gene–drug interactions across seven

    更新日期:2020-10-19
  • A MYC and RAS co-activation signature in localized prostate cancer drives bone metastasis and castration resistance
    Nat. Cancer Pub Date : 2020-10-19
    Juan M. Arriaga; Sukanya Panja; Mohammed Alshalalfa; Junfei Zhao; Min Zou; Arianna Giacobbe; Chioma J. Madubata; Jaime Yeji Kim; Antonio Rodriguez; Ilsa Coleman; Renu K. Virk; Hanina Hibshoosh; Onur Ertunc; Büşra Ozbek; Julia Fountain; R. Jeffrey Karnes; Jun Luo; Emmanuel S. Antonarakis; Peter S. Nelson; Felix Y. Feng; Mark A. Rubin; Angelo M. De Marzo; Raul Rabadan; Peter A. Sims; Antonina Mitrofanova;

    Understanding the intricacies of lethal prostate cancer poses specific challenges due to difficulties in accurate modeling of metastasis in vivo. Here we show that NPKEYFP mice (for Nkx3.1CreERT2/+; Ptenflox/flox; KrasLSL-G12D/+; R26R-CAG-LSL-EYFP/+) develop prostate cancer with a high penetrance of metastasis to bone, thereby enabling detection and tracking of bone metastasis in vivo and ex vivo.

    更新日期:2020-10-19
  • Optimizing CARs for ocular delivery
    Nat. Cancer Pub Date : 2020-10-12
    Anandani Nellan; Terry J. Fry

    Effective methods for treating retinoblastoma while preserving vision are an unmet clinical need. Subretinal delivery of a hydrogel containing T cells that secrete the cytokine IL-15 and express a chimeric antigen receptor directed at the ganglioside protein GD2 completely controls retinoblastoma in immunocompromised mice, with no obvious damage to the surrounding retina.

    更新日期:2020-10-12
  • GD2-specific CAR T cells encapsulated in an injectable hydrogel control retinoblastoma and preserve vision
    Nat. Cancer Pub Date : 2020-10-12
    Kai Wang; Yuhui Chen; Sarah Ahn; Min Zheng; Elisa Landoni; Gianpietro Dotti; Barbara Savoldo; Zongchao Han

    Retinoblastoma (RB) is a pediatric retinal tumor that overexpresses the ganglioside GD2. Although it is treatable in patients with early diagnosis, patients may lose one or two eyes. We generated GD2-specific chimeric antigen receptor T lymphocytes (GD2.CAR-Ts) and locally delivered them to mice with an in situ grafting RB. We showed that, when used in combination with the local release of interleukin-15

    更新日期:2020-10-12
  • FoxM1 insufficiency hyperactivates Ect2–RhoA–mDia1 signaling to drive cancer
    Nat. Cancer Pub Date : 2020-10-12
    Jazeel F. Limzerwala; Karthik B. Jeganathan; Jake A. Kloeber; Brian A. Davies; Cheng Zhang; Ines Sturmlechner; Jian Zhong; Raul Fierro Velasco; Alan P. Fields; Yaxia Yuan; Darren J. Baker; Daohong Zhou; Hu Li; David J. Katzmann; Jan M. van Deursen

    FoxM1 activates genes that regulate S–G2–M cell-cycle progression and, when overexpressed, is associated with poor clinical outcome in multiple cancers. Here we identify FoxM1 as a tumor suppressor in mice that, through its N-terminal domain, binds to and inhibits Ect2 to limit the activity of RhoA GTPase and its effector mDia1, a catalyst of cortical actin nucleation. FoxM1 insufficiency impedes centrosome

    更新日期:2020-10-12
  • A global effort to understand the riddles of COVID-19 and cancer
    Nat. Cancer Pub Date : 2020-10-09
    Vivek Subbiah

    Cancer has found a formidable foil in COVID-19, and this has brought to the fore the early concerns that COVID-19 could have a deeper impact on oncology patients. Two studies now provide insights into the enigma surrounding the determinants of the worsening of COVID-19 symptoms in patients with cancer.

    更新日期:2020-10-11
  • What next for postdocs?
    Nat. Cancer Pub Date : 2020-10-09

    Postdoctoral researchers face substantial challenges and stresses that have been exacerbated by the COVID-19 pandemic. Positive action is needed from research institutions, funders and individual investigators to support postdocs and fortify the research endeavor.

    更新日期:2020-10-11
  • The immuno-oncological challenge of COVID-19
    Nat. Cancer Pub Date : 2020-10-02
    Lisa Derosa; Cléa Melenotte; Franck Griscelli; Bertrand Gachot; Aurélien Marabelle; Guido Kroemer; Laurence Zitvogel

    Coronavirus disease 2019 (COVID-19) and its causative virus, SARS-CoV-2, pose considerable challenges for the management of oncology patients. COVID-19 presents as a particularly severe respiratory and systemic infection in aging and immunosuppressed individuals, including patients with cancer. Moreover, severe COVID-19 is linked to an inflammatory burst and lymphopenia, which may aggravate cancer

    更新日期:2020-10-02
  • Author Correction: L1CAM defines the regenerative origin of metastasis-initiating cells in colorectal cancer
    Nat. Cancer Pub Date : 2020-09-30
    Karuna Ganesh; Harihar Basnet; Yasemin Kaygusuz; Ashley M. Laughney; Lan He; Roshan Sharma; Kevin P. O’Rourke; Vincent P. Reuter; Yun-Han Huang; Mesruh Turkekul; Ekrem Emrah Er; Ignas Masilionis; Katia Manova-Todorova; Martin R. Weiser; Leonard B. Saltz; Julio Garcia-Aguilar; Richard Koche; Scott W. Lowe; Dana Pe’er; Jinru Shia; Joan Massagué

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

    更新日期:2020-09-30
  • Metabolic adaptation of acute lymphoblastic leukemia to the central nervous system microenvironment depends on stearoyl-CoA desaturase
    Nat. Cancer Pub Date : 2020-09-28
    Angela Maria Savino; Sara Isabel Fernandes; Orianne Olivares; Anna Zemlyansky; Antony Cousins; Elke K. Markert; Shani Barel; Ifat Geron; Liron Frishman; Yehudit Birger; Cornelia Eckert; Sergey Tumanov; Gillian MacKay; Jurre J. Kamphorst; Pawel Herzyk; Jonatan Fernández-García; Ifat Abramovich; Inbal Mor; Michela Bardini; Ersilia Barin; Sudha Janaki-Raman; Justin R. Cross; Michael G. Kharas; Eyal Gottlieb;

    Metabolic reprogramming is a key hallmark of cancer, but less is known about metabolic plasticity of the same tumor at different sites. Here, we investigated the metabolic adaptation of leukemia in two different microenvironments, the bone marrow and the central nervous system (CNS). We identified a metabolic signature of fatty acid synthesis in CNS leukemia, highlighting stearoyl-CoA desaturase (SCD)

    更新日期:2020-09-28
  • Determinants of the outcomes of patients with cancer infected with SARS-CoV-2: results from the Gustave Roussy cohort
    Nat. Cancer Pub Date : 2020-09-22
    Laurence Albiges; Stéphanie Foulon; Arnaud Bayle; Bertrand Gachot; Fanny Pommeret; Christophe Willekens; Annabelle Stoclin; Mansouria Merad; Frank Griscelli; Ludovic Lacroix; Florence Netzer; Thomas Hueso; Corinne Balleyguier; Samy Ammari; Emeline Colomba; Giulia Baciarello; Audrey Perret; Antoine Hollebecque; Julien Hadoux; Jean-Marie Michot; Nathalie Chaput; Veronique Saada; Mathilde Hauchecorne;

    Patients with cancer are presumed to be at increased risk of severe COVID-19 outcomes due to underlying malignancy and treatment-induced immunosuppression. Of the first 178 patients managed for COVID-19 at the Gustave Roussy Cancer Centre, 125 (70.2%) were hospitalized, 47 (26.4%) developed clinical worsening and 31 (17.4%) died. An age of over 70 years, smoking status, metastatic disease, cytotoxic

    更新日期:2020-09-22
  • Age-associated mitochondrial DNA mutations cause metabolic remodeling that contributes to accelerated intestinal tumorigenesis
    Nat. Cancer Pub Date : 2020-09-21
    Anna L. M. Smith; Julia C. Whitehall; Carla Bradshaw; David Gay; Fiona Robertson; Alasdair P. Blain; Gavin Hudson; Angela Pyle; David Houghton; Matthew Hunt; James N. Sampson; Craig Stamp; Grace Mallett; Shoba Amarnath; Jack Leslie; Fiona Oakley; Laura Wilson; Angela Baker; Oliver M. Russell; Riem Johnson; Claire A. Richardson; Bhavana Gupta; Iain McCallum; Stuart A. C. McDonald; Seamus Kelly; John

    Oxidative phosphorylation (OXPHOS) defects caused by somatic mitochondrial DNA mutations increase with age in human colorectal epithelium and are prevalent in colorectal tumors, but whether they actively contribute to tumorigenesis remains unknown. Here we demonstrate that mitochondrial DNA mutations causing OXPHOS defects are enriched during the human adenoma/carcinoma sequence, suggesting that they

    更新日期:2020-09-21
  • Tailoring immunotherapy with liquid biopsy
    Nat. Cancer Pub Date : 2020-09-18
    Jeanne Tie

    Immunotherapy has changed the treatment paradigm for patients with cancer, but patient selection, response assessment and treatment duration require further refinement. A recent study reports that the kinetics of circulating tumor DNA reflect response and resistance to immunotherapy treatment across multiple cancer types and could be used to tailor treatment.

    更新日期:2020-09-20
  • Autophagy promotes growth of tumors with high mutational burden by inhibiting a T-cell immune response
    Nat. Cancer Pub Date : 2020-09-18
    Laura Poillet-Perez; Daniel W. Sharp; Yang Yang; Saurabh V. Laddha; Maria Ibrahim; Praveen K. Bommareddy; Zhixian Sherrie Hu; Joshua Vieth; Michael Haas; Marcus W. Bosenberg; Joshua D. Rabinowitz; Jian Cao; Jun-Lin Guan; Shridar Ganesan; Chang S. Chan; Janice M. Mehnert; Edmund C. Lattime; Eileen White

    Macroautophagy (hereafter autophagy) degrades and recycles intracellular components to sustain metabolism and survival during starvation. Host autophagy promotes tumor growth by providing essential tumor nutrients. Autophagy also regulates immune cell homeostasis and function and suppresses inflammation. Although host autophagy does not promote a T-cell antitumor immune response in tumors with low

    更新日期:2020-09-20
  • ASS1igning purine dependency to cancer
    Nat. Cancer Pub Date : 2020-09-03
    Elodie Villa; Issam Ben-Sahra

    The urea cycle enzyme argininosuccinate synthase 1 (ASS1) is upregulated in some cancer types. A study now shows that tumor cells with elevated urea cycle activity due to high ASS1 expression enhance gluconeogenesis, enabling a metabolic shift toward serine synthesis and causing purine synthesis addiction for growth and proliferation.

    更新日期:2020-09-20
  • 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

    更新日期:2020-09-14
  • 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

    更新日期:2020-09-14
  • 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.

    更新日期:2020-09-11
  • 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

    更新日期:2020-09-08
  • 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

    更新日期:2020-08-31
  • 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.

    更新日期:2020-08-22
  • 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.

    更新日期:2020-08-18
  • 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.

    更新日期:2020-08-18
  • 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

    更新日期:2020-08-18
  • 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

    更新日期:2020-08-18
  • 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.

    更新日期:2020-08-10
  • 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)

    更新日期:2020-08-10
  • 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

    更新日期:2020-08-10
  • 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

    更新日期:2020-08-03
  • 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

    更新日期:2020-07-31
  • 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.

    更新日期:2020-07-27
  • 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

    更新日期:2020-07-27
  • 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

    更新日期:2020-07-27
  • 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.

    更新日期:2020-07-21
  • 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

    更新日期:2020-07-20
  • 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.

    更新日期:2020-07-10
  • 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

    更新日期:2020-07-06
  • 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

    更新日期:2020-07-06
  • 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

    更新日期:2020-07-06
  • 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

    更新日期:2020-06-29
  • 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.

    更新日期:2020-06-23
  • 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

    更新日期:2020-06-23