Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment.

Cancer Cell
David A WheelerLouis M Staudt

Abstract

A small fraction of cancer patients with advanced disease survive significantly longer than patients with clinically comparable tumors. Molecular mechanisms for exceptional responses to therapy have been identified by genomic analysis of tumor biopsies from individual patients. Here, we analyzed tumor biopsies from an unbiased cohort of 111 exceptional responder patients using multiple platforms to profile genetic and epigenetic aberrations as well as the tumor microenvironment. Integrative analysis uncovered plausible mechanisms for the therapeutic response in nearly a quarter of the patients. The mechanisms were assigned to four broad categories-DNA damage response, intracellular signaling, immune engagement, and genetic alterations characteristic of favorable prognosis-with many tumors falling into multiple categories. These analyses revealed synthetic lethal relationships that may be exploited therapeutically and rare genetic lesions that favor therapeutic success, while also providing a wealth of testable hypotheses regarding oncogenic mechanisms that may influence the response to cancer therapy.

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Citations

Feb 18, 2021·Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer·Stephen SonisJoel Epstein
May 21, 2021·Journal of the American Chemical Society·Shelby C YuhasMarc M Greenberg
May 28, 2021·British Journal of Cancer·Allan Michael Jordan
May 28, 2021·JCO Oncology Practice·Katie KanterAparna R Parikh
May 25, 2021·Frontiers in Oncology·Fangyuan LiuPeng Du
Jul 2, 2021·Frontiers in Cell and Developmental Biology·Elena Navarro-Carrasco, Pedro A Lazo
Jul 22, 2021·Nature Reviews. Clinical Oncology·Mariana Paes DiasJos Jonkers
Aug 21, 2021·Briefings in Bioinformatics·Anson T KuAdam G Sowalsky
Sep 21, 2021·Frontiers in Cell and Developmental Biology·Ignacio Campillo-MarcosPedro A Lazo

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