An expanded universe of cancer targets

William C Hahn; Joel S Bader; Theodore P Braun; Andrea Califano; Paul A Clemons; Brian J Druker; Andrew J Ewald; Haian Fu; Subhashini Jagu; Christopher J Kemp; William Kim; Calvin J Kuo; Michael McManus; Gordon B Mills; Xiulei Mo; Nidhi Sahni; Stuart L Schreiber; Jessica A Talamas; Pablo Tamayo; Jeffrey W Tyner; Bridget K Wagner; William A Weiss; Daniela S Gerhard; Cancer Target Discovery and Development Network

doi:10.1016/j.cell.2021.02.020

An expanded universe of cancer targets

Cell. 2021 Mar 4;184(5):1142-1155. doi: 10.1016/j.cell.2021.02.020.

Authors

William C Hahn¹, Joel S Bader², Theodore P Braun³, Andrea Califano⁴, Paul A Clemons⁵, Brian J Druker³, Andrew J Ewald⁶, Haian Fu⁷, Subhashini Jagu⁸, Christopher J Kemp⁹, William Kim¹⁰, Calvin J Kuo¹¹, Michael McManus¹², Gordon B Mills¹³, Xiulei Mo⁷, Nidhi Sahni¹⁴, Stuart L Schreiber⁵, Jessica A Talamas¹⁵, Pablo Tamayo¹⁰, Jeffrey W Tyner¹⁶, Bridget K Wagner⁵, William A Weiss¹⁷, Daniela S Gerhard⁸; Cancer Target Discovery and Development Network

Collaborators

Cancer Target Discovery and Development Network:
Vlado Dancik, Shubhroz Gill, Bruce Hua, Tanaz Sharifnia, Vasanthi Viswanathan, Yilong Zou, Filemon Dela Cruz, Andrew Kung, Brent Stockwell, Jesse Boehm, Josh Dempster, Robert Manguso, Francisca Vazquez, Lee A D Cooper, Yuhong Du, Andrey Ivanov, Sagar Lonial, Carlos S Moreno, Qiankun Niu, Taofeek Owonikoko, Suresh Ramalingam, Matthew Reyna, Wei Zhou, Carla Grandori, Ilya Shmulevich, Elizabeth Swisher, Jitong Cai, Issac S Chan, Matthew Dunworth, Yuchen Ge, Dan Georgess, Eloïse M Grasset, Elodie Henriet, Hildur Knútsdóttir, Michael G Lerner, Veena Padmanaban, Matthew C Perrone, Yasir Suhail, Yohannes Tsehay, Manisha Warrier, Quin Morrow, Tamilla Nechiporuk, Nicola Long, Jennifer Saultz, Andy Kaempf, Jessica Minnier, Cristina E Tognon, Stephen E Kurtz, Anupriya Agarwal, Jordana Brown, Kevin Watanabe-Smith, Tania Q Vu, Thomas Jacob, Yunqi Yan, Bridget Robinson, Evan F Lind, Yoko Kosaka, Emek Demir, Joseph Estabrook, Michael Grzadkowski, Olga Nikolova, Ken Chen, Ben Deneen, Han Liang, Michael C Bassik, Asmita Bhattacharya, Kevin Brennan, Christina Curtis, Olivier Gevaert, Hanlee P Ji, Kasper A J Karlsson, Kremena Karagyozova, Yuan-Hung Lo, Katherine Liu, Michitaka Nakano, Anuja Sathe, Amber R Smith, Kaitlyn Spees, Wing Hing Wong, Kanako Yuki, Matt Hangauer, Dan S Kaufman, Allan Balmain, Saumya R Bollam, Wei-Ching Chen, QiWen Fan, Kelly Kersten, Matthew Krummel, Yun Rose Li, Marie Menard, Nicole Nasholm, Christin Schmidt, Nina K Serwas, Hiroyuki Yoda

Affiliations

¹ Dana-Farber Cancer Institute, Department of Medical Oncology, 450 Brookline Avenue, Boston, MA, USA. Electronic address: william_hahn@dfci.harvard.edu.
² Department of Biomedical Engineering and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
³ Knight Cancer Institute and Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR, USA.
⁴ Department of Systems Biology, Biomedical Informatics, Biochemistry and Molecular Biophysics, and Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.
⁵ Broad Institute, 415 Main Street, Cambridge, MA, USA.
⁶ Department of Cell Biology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
⁷ Department of Pharmacology and Chemical Biology, Emory Chemical Biology Discovery Center, and Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
⁸ Office of Cancer Genomics, Center for Cancer Genomics, National Cancer Institute, NIH, Bethesda, MD, USA.
⁹ Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
¹⁰ Moores Cancer Center, Center for Novel Therapeutics and Department of Medicine, UC San Diego, La Jolla, CA, USA.
¹¹ Hematology Division, Stanford University School of Medicine, Stanford, CA, USA.
¹² Department of Microbiology and Immunology, UCSF Diabetes Center, and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
¹³ Department of Cell, Development and Cancer Biology, Knight Cancer Institute, Oregon Health and Sciences University, Portland, OR, USA.
¹⁴ Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, USA.
¹⁵ Dana-Farber Cancer Institute, Department of Medical Oncology, 450 Brookline Avenue, Boston, MA, USA.
¹⁶ Knight Cancer Institute, Oregon Health & Science University and Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR, USA.
¹⁷ Departments of Neurology, Neurological Surgery, Pediatrics, and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.

Abstract

The characterization of cancer genomes has provided insight into somatically altered genes across tumors, transformed our understanding of cancer biology, and enabled tailoring of therapeutic strategies. However, the function of most cancer alleles remains mysterious, and many cancer features transcend their genomes. Consequently, tumor genomic characterization does not influence therapy for most patients. Approaches to understand the function and circuitry of cancer genes provide complementary approaches to elucidate both oncogene and non-oncogene dependencies. Emerging work indicates that the diversity of therapeutic targets engendered by non-oncogene dependencies is much larger than the list of recurrently mutated genes. Here we describe a framework for this expanded list of cancer targets, providing novel opportunities for clinical translation.

Publication types

Research Support, N.I.H., Extramural
Review

MeSH terms

Animals
Clinical Trials as Topic
Disease Models, Animal
Drug Delivery Systems*
Genomics
Humans
Neoplasms / drug therapy*
Neoplasms / genetics
Neoplasms / pathology
Tumor Escape / drug effects
Tumor Microenvironment / drug effects

Abstract

Publication types

MeSH terms

Grants and funding