Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment.
Cancer Cell
; 39(1): 38-53.e7, 2021 01 11.
Article
em En
| MEDLINE
| ID: mdl-33217343
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.
Palavras-chave
DNA methylation analysis; DNA repair mechanisms; N of 1 experiment; RNA sequencing; combination cancer therapy; exceptional response to therapy; integrating molecular and clinical data; multi-platform genomic analyses; precision cancer medicine; rare mutations; synthetic lethality; whole-exome sequencing
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Genômica
/
Redes Reguladoras de Genes
/
Neoplasias
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Cancer Cell
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos