Identification of targeted therapy options for gastric adenocarcinoma by comprehensive analysis of genomic data.
Gastric Cancer
; 23(4): 627-638, 2020 07.
Article
em En
| MEDLINE
| ID: mdl-32107691
ABSTRACT
BACKGROUND:
So far only trastuzumab, pembrolizumab and ramucirumab have been approved by the FDA for targeted therapy in gastric cancer (GC). Here we report on potential targeted therapy options for gastric adenocarcinoma based on a novel analysis of "The Cancer Genome Atlas (TCGA)" database.METHODS:
One hundred two FDA-approved targeted cancer drugs were compiled and molecular targets defined. Drugs were considered as potentially effective if targeted genes showed (1) an increase in copy number, (2) gain of function with oncogene activation, (3) specific alterations responsive to approved drugs. Additionally, genetic changes that confer drug resistance and/or sensitivity were evaluated.RESULTS:
Fifty percentage of patients with GC may be treatable with non-GC but FDA-approved targeted cancer therapies. The major drug identified in our in silico study for GC is copanlisib, a PI3K inhibitor. In the TCGA patient database, our genetically based drug response prediction identified more patients with alterations sensitive to copanlisib compared to the already-GC-approved drug trastuzumab (20%, 78 out of 393 patients, vs. trastuzumab 13%, 52 of 393 patients), which is mainly due to the high incidence of PIK3CA gain of function mutations within mutation hot spots.CONCLUSION:
Our results demonstrate that various currently FDA-approved drugs might be candidates for targeted therapy of GC. For clinical trials, cancer patients should be selected based on the genomic profile of their tumor.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
/
Adenocarcinoma
/
Biomarcadores Tumorais
/
Resistencia a Medicamentos Antineoplásicos
/
Genômica
/
Terapia de Alvo Molecular
/
Antineoplásicos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Gastric Cancer
Assunto da revista:
GASTROENTEROLOGIA
/
NEOPLASIAS
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Alemanha