Advertisement

Table of Contents

In This Issue

  • In This Issue
    In This Issue
    Cancer Discov February 1 2021 11 (2) 211-213; DOI:10.1158/2159-8290.CD-ITI11-2

In the Spotlight

Science in Society

In Focus

Reviews

Research Briefs

  • Research Briefs | AuthorChoice
    Somatic HLA Class I Loss Is a Widespread Mechanism of Immune Evasion Which Refines the Use of Tumor Mutational Burden as a Biomarker of Checkpoint Inhibitor Response
    Meagan Montesion, Karthikeyan Murugesan, Dexter X. Jin, Radwa Sharaf, Nora Sanchez, Ameet Guria, Max Minker, Gerald Li, Virginia Fisher, Ethan S. Sokol, Dean C. Pavlick, Jay A. Moore, Alan Braly, Gaurav Singal, David Fabrizio, Leah A. Comment, Naiyer A. Rizvi, Brian M. Alexander, Garrett M. Frampton, Priti S. Hegde and Lee A. Albacker
    Cancer Discov February 1 2021 11 (2) 282-292; DOI:10.1158/2159-8290.CD-20-0672

    Across cancer types, loss of heterozygosity at the locus encoding HLA-I was an independent prognostic factor for response to immune checkpoint blockade, and its predictive power improved when combined with measures of tumor mutation burden.

  • Research Briefs | AuthorChoice
    Lower Airway Dysbiosis Affects Lung Cancer Progression
    Jun-Chieh J. Tsay, Benjamin G. Wu, Imran Sulaiman, Katherine Gershner, Rosemary Schluger, Yonghua Li, Ting-An Yie, Peter Meyn, Evan Olsen, Luisannay Perez, Brendan Franca, Joseph Carpenito, Tadasu Iizumi, Mariam El-Ashmawy, Michelle Badri, James T. Morton, Nan Shen, Linchen He, Gaetane Michaud, Samaan Rafeq, Jamie L. Bessich, Robert L. Smith, Harald Sauthoff, Kevin Felner, Ray Pillai, Anastasia-Maria Zavitsanou, Sergei B. Koralov, Valeria Mezzano, Cynthia A. Loomis, Andre L. Moreira, William Moore, Aristotelis Tsirigos, Adriana Heguy, William N. Rom, Daniel H. Sterman, Harvey I. Pass, Jose C. Clemente, Huilin Li, Richard Bonneau, Kwok-Kin Wong, Thales Papagiannakopoulos and Leopoldo N. Segal
    Cancer Discov February 1 2021 11 (2) 293-307; DOI:10.1158/2159-8290.CD-20-0263

    Lower airway dysbiosis characterized by excessive colonization with oral commensal microbes, particularly Veillonella parvula, was a predictor of poor prognosis in lung cancer, and in vivo experiments supported a role for V. parvula colonization in decreasing survival.

Research Articles

  • Research Articles | AuthorChoice
    Personalized Antibodies for Gastroesophageal Adenocarcinoma (PANGEA): A Phase II Study Evaluating an Individualized Treatment Strategy for Metastatic Disease
    Daniel V.T. Catenacci, Stephanie Moya, Samantha Lomnicki, Leah M. Chase, Bryan F. Peterson, Natalie Reizine, Lindsay Alpert, Namrata Setia, Shu-Yuan Xiao, John Hart, Uzma D. Siddiqui, D. Kyle Hogarth, Oliver S. Eng, Kiran Turaga, Kevin Roggin, Mitchell C. Posner, Paul Chang, Sunil Narula, Murtuza Rampurwala, Yuan Ji, Theodore Karrison, Chih-Yi Liao, Blase N. Polite and Hedy L. Kindler
    Cancer Discov February 1 2021 11 (2) 308-325; DOI:10.1158/2159-8290.CD-20-1408

    In a phase II clinical trial, personalized antibodies plus molecularly targeted chemotherapy improved median overall survival and the one-year survival rate in patients with gastroesophageal adenocarcinoma relative to historical survival data.

  • Research Articles | AuthorChoice
    Clinicogenomic Analysis of FGFR2-Rearranged Cholangiocarcinoma Identifies Correlates of Response and Mechanisms of Resistance to Pemigatinib
    Ian M. Silverman, Antoine Hollebecque, Luc Friboulet, Sherry Owens, Robert C. Newton, Huiling Zhen, Luis Féliz, Camilla Zecchetto, Davide Melisi and Timothy C. Burn
    Cancer Discov February 1 2021 11 (2) 326-339; DOI:10.1158/2159-8290.CD-20-0766

    In patients with cholangiocarcinoma harboring FGFR fusions or rearrangements, response to the FGFR1–3 inhibitor was equally likely regardless of the type of genomic alteration, and resistance mutations affected the FGFR2 kinase domain.

  • Research Articles | AuthorChoice
    Selection of Oncogenic Mutant Clones in Normal Human Skin Varies with Body Site
    Joanna C. Fowler, Charlotte King, Christopher Bryant, Michael W.J. Hall, Roshan Sood, Swee Hoe Ong, Eleanor Earp, David Fernandez-Antoran, Jonas Koeppel, Stefan C. Dentro, David Shorthouse, Amer Durrani, Kate Fife, Edward Rytina, Doreen Milne, Amit Roshan, Krishnaa Mahububani, Kourosh Saeb-Parsy, Benjamin A. Hall, Moritz Gerstung and Philip H. Jones
    Cancer Discov February 1 2021 11 (2) 340-361; DOI:10.1158/2159-8290.CD-20-1092

    Genetic analyses of healthy aged human epidermal cells revealed skin site–specific mutational signatures, with common skin cancer sites exhibiting more potentially oncogenic mutations and with high variability in mutations under positive selection among sites.

  • Research Articles | AuthorChoice
    Genetically Defined, Syngeneic Organoid Platform for Developing Combination Therapies for Ovarian Cancer
    Shuang Zhang, Sonia Iyer, Hao Ran, Igor Dolgalev, Shengqing Gu, Wei Wei, Connor J.R. Foster, Cynthia A. Loomis, Narciso Olvera, Fanny Dao, Douglas A. Levine, Robert A. Weinberg and Benjamin G. Neel
    Cancer Discov February 1 2021 11 (2) 362-383; DOI:10.1158/2159-8290.CD-20-0455

    Organoids representing high-grade serous ovarian cancer were developed; these organoids exhibited varying sensitivities to chemotherapy drugs and elicited different immune responses, suggesting they may serve as a novel platform for discovery.

  • Research Articles | AuthorChoice
    Genetically Defined Syngeneic Mouse Models of Ovarian Cancer as Tools for the Discovery of Combination Immunotherapy
    Sonia Iyer, Shuang Zhang, Simge Yucel, Heiko Horn, Sean G. Smith, Ferenc Reinhardt, Esmee Hoefsmit, Bimarzhan Assatova, Julia Casado, Marie-Charlotte Meinsohn, M. Inmaculada Barrasa, George W. Bell, Fernando Pérez-Villatoro, Kaisa Huhtinen, Johanna Hynninen, Jaana Oikkonen, Pamoda M. Galhenage, Shailja Pathania, Paula T. Hammond, Benjamin G. Neel, Anniina Farkkila, David Pépin and Robert A. Weinberg
    Cancer Discov February 1 2021 11 (2) 384-407; DOI:10.1158/2159-8290.CD-20-0818

    To address the inability of current high-grade serous tubo-ovarian carcinoma models to accurately recapitulate immunotherapy responses, a new mouse model was developed; proof-of concept experiments uncovered follistatin as a mediator of response.

  • Research Articles
    A TLR3 Ligand Reestablishes Chemotherapeutic Responses in the Context of FPR1 Deficiency
    Julie Le Naour, Peng Liu, Liwei Zhao, Sandy Adjemian, Zsofia Sztupinszki, Julien Taieb, Claire Mulot, Aymeric Silvin, Charles-Antoine Dutertre, Florent Ginhoux, Allan Sauvat, Giulia Cerrato, Francesca Castoldi, Isabelle Martins, Gautier Stoll, Juliette Paillet, Khady Mangane, Cornelia Richter, Oliver Kepp, Maria Chiara Maiuri, Federico Pietrocola, Peter Vandenabeele, Fabrice André, Suzette Delaloge, Zoltan Szallasi, Pierre Laurent-Puig, Jessica Zucman-Rossi, Laurence Zitvogel, Jonathan G. Pol, Erika Vacchelli and Guido Kroemer
    Cancer Discov February 1 2021 11 (2) 408-423; DOI:10.1158/2159-8290.CD-20-0465

    The TLR3 ligand polyinosinic:polycytidylic acid improved the efficacy of chemotherapy observed in the context of FPR1 loss-of-function mutation, which occurs in 30% of individuals and diminishes the antitumor immune response following chemotherapy.

  • Research Articles
    Timed Ang2-Targeted Therapy Identifies the Angiopoietin–Tie Pathway as Key Regulator of Fatal Lymphogenous Metastasis
    Nicolas Gengenbacher, Mahak Singhal, Carolin Mogler, Ling Hai, Laura Milde, Ashik Ahmed Abdul Pari, Eva Besemfelder, Claudine Fricke, Daniel Baumann, Stephanie Gehrs, Jochen Utikal, Moritz Felcht, Junhao Hu, Matthias Schlesner, Rienk Offringa, Sudhakar R. Chintharlapalli and Hellmut G. Augustin
    Cancer Discov February 1 2021 11 (2) 424-445; DOI:10.1158/2159-8290.CD-20-0122

    A hindrance to the study of metastasis via lymphatic vessels with lymph nodes as intermediate sites was overcome using a genetically engineered mouse model–derived allograft model, the use of which uncovered the Ang2–Tie2 pathway as a critical dependency.

  • Research Articles
    Netrin G1 Promotes Pancreatic Tumorigenesis through Cancer-Associated Fibroblast–Driven Nutritional Support and Immunosuppression
    Ralph Francescone, Débora Barbosa Vendramini-Costa, Janusz Franco-Barraza, Jessica Wagner, Alexander Muir, Allison N. Lau, Linara Gabitova, Tatiana Pazina, Sapna Gupta, Tiffany Luong, Dustin Rollins, Ruchi Malik, Roshan J. Thapa, Diana Restifo, Yan Zhou, Kathy Q. Cai, Harvey H. Hensley, Yinfei Tan, Warren D. Kruger, Karthik Devarajan, Siddharth Balachandran, Andres J. Klein-Szanto, Huamin Wang, Wafik S. El-Deiry, Matthew G. Vander Heiden, Suraj Peri, Kerry S. Campbell, Igor Astsaturov and Edna Cukierman
    Cancer Discov February 1 2021 11 (2) 446-479; DOI:10.1158/2159-8290.CD-20-0775

    The glutamatergic presynaptic protein Netrin-G1 was found to be a major contributor to the metabolic and immunosuppressive tumor microenvironment in pancreatic ductal adenocarcinoma, and blocking Netrin-G1 in vivo suppressed tumorigenesis.

  • Research Articles
    The RNA m6A Reader YTHDF2 Maintains Oncogene Expression and Is a Targetable Dependency in Glioblastoma Stem Cells
    Deobrat Dixit, Briana C. Prager, Ryan C. Gimple, Hui Xian Poh, Yang Wang, Qiulian Wu, Zhixin Qiu, Reilly L. Kidwell, Leo J.Y. Kim, Qi Xie, Kristoffer Vitting-Seerup, Shruti Bhargava, Zhen Dong, Li Jiang, Zhe Zhu, Petra Hamerlik, Samie R. Jaffrey, Jing Crystal Zhao, Xiuxing Wang and Jeremy N. Rich
    Cancer Discov February 1 2021 11 (2) 480-499; DOI:10.1158/2159-8290.CD-20-0331

    In glioblastoma stem cells, YTHDF2 (which reads mRNA for the modified nucleotide N6-methyladenosine) stabilized MYC and VEGFA transcripts via an IGFBP3-mediated mechanism, and blocking IGF–IGF1R signaling in vivo hindered glioblastoma growth.

  • Research Articles | AuthorChoice
    The Hepatic Microenvironment Uniquely Protects Leukemia Cells through Induction of Growth and Survival Pathways Mediated by LIPG
    Haobin Ye, Mohammad Minhajuddin, Anna Krug, Shanshan Pei, Chih-Hsing Chou, Rachel Culp-Hill, Jessica Ponder, Erik De Bloois, Björn Schniedewind, Maria L. Amaya, Anagha Inguva, Brett M. Stevens, Daniel A. Pollyea, Uwe Christians, H. Leighton Grimes, Angelo D'Alessandro and Craig T. Jordan
    Cancer Discov February 1 2021 11 (2) 500-519; DOI:10.1158/2159-8290.CD-20-0318

    Liver-infiltrating leukemia stem cells in mice acquired a proliferative, chemotherapy-resistant phenotype characterized by overexpression of the gene encoding the lipase LIPG, which was sufficient to induce the same phenotype in non–liver-infiltrating leukemia cells.

News in Brief

News in Depth

Research Watch

Correction

Back to top

Jump to

Advertisement