Identification of targeted therapy options for gastric adenocarcinoma by comprehensive analysis of genomic data
| Autor: | Hakan Alakus, Daniel A. Hescheler, Maximilian Michel, Thomas Zander, Alexander Quaas, M. Korenkov, Patrick Sven Plum, A Gassa, Christiane J. Bruns |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Drug Oncology Cancer Research medicine.medical_specialty medicine.medical_treatment media_common.quotation_subject New treatment advances Stomach neoplasms Antineoplastic Agents Pembrolizumab Drug resistance Targeted molecular therapy Adenocarcinoma Targeted therapy Ramucirumab 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Trastuzumab Targeted Molecular Therapy Internal medicine Human genome project Biomarkers Tumor medicine Humans Molecular Targeted Therapy Copanlisib media_common Genome Human business.industry Gastroenterology Genomics General Medicine Prognosis 030104 developmental biology chemistry Drug Resistance Neoplasm 030220 oncology & carcinogenesis Original Article Transcriptome business medicine.drug |
| Zdroj: | Gastric Cancer |
| ISSN: | 1436-3305 1436-3291 |
| Popis: | BackgroundSo 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.MethodsOne 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.ResultsFifty 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.ConclusionOur 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. |
| Databáze: | OpenAIRE |
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