Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment.

TitleMolecular Features of Cancers Exhibiting Exceptional Responses to Treatment.
Publication TypeJournal Article
Year of Publication2021
AuthorsWheeler, DA, Takebe, N, Hinoue, T, Hoadley, KA, Cardenas, MF, Hamilton, AM, Laird, PW, Wang, L, Johnson, A, Dewal, N, Miller, V, Piñeyro, D, de Moura, MCastro, Esteller, M, Shen, H, Zenklusen, JClaude, Tarnuzzer, R, McShane, LM, Tricoli, JV, Williams, PM, Lubensky, I, O'Sullivan-Coyne, G, Kohn, EC, Little, RF, White, J, Malik, S, Harris, L, Weil, C, Chen, AP, Karlovich, C, Rodgers, B, Shankar, L, Jacobs, P, Nolan, T, Hu, J, Muzny, DM, Doddapaneni, H, Korchina, V, Gastier-Foster, J, Bowen, J, Leraas, K, Edmondson, EF, Doroshow, JH, Conley, BA, S Ivy, P, Staudt, LM
JournalCancer Cell
Date Published2021 Jan 11
KeywordsAntineoplastic Agents, Biopsy, Epigenesis, Genetic, Female, Gene Regulatory Networks, Genetic Variation, Genomics, Humans, Male, Neoplasms, Prognosis, Survival Analysis, Treatment Outcome, Tumor Microenvironment

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.

Alternate JournalCancer Cell
PubMed ID33217343
PubMed Central IDPMC8478080
Grant ListP30 ES010126 / ES / NIEHS NIH HHS / United States
T32 GM122741 / GM / NIGMS NIH HHS / United States
U24 CA143843 / CA / NCI NIH HHS / United States
Z99 CA999999 / ImNIH / Intramural NIH HHS / United States
HHSN261201700005I / CA / NCI NIH HHS / United States
HHSN261200800001C / RC / CCR NIH HHS / United States
HHSN261201700005C / CA / NCI NIH HHS / United States
HHSN261200800001E / CA / NCI NIH HHS / United States
U24 CA210969 / CA / NCI NIH HHS / United States
U24 CA210988 / CA / NCI NIH HHS / United States

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