A transcriptomics approach to expand therapeutic options and optimize clinical trials in oncology

• Published in: Therapeutic advances in medical oncology 2023-01, Vol.15, p.17588359231156382-17588359231156382
• Main Authors: Lazar, Vladimir, Zhang, Baolin, Magidi, Shai, Le Tourneau, Christophe, Raymond, Eric, Ducreux, Michel, Bresson, Catherine, Raynaud, Jacques, Wunder, Fanny, Onn, Amir, Felip, Enriqueta, Tabernero, Josep, Batist, Gerald, Kurzrock, Razelle, Rubin, Eitan, Schilsky, Richard L.
• Format: Article
• Language: English
• Subjects: c-Met protein; Clinical trials; CTLA-4 protein; Drug development; Gene expression; Immunosuppressive agents; Immunotherapy; Metastases; Metastasis; Oncology; Patients; PD-L1 protein; Precision medicine; Solid tumors; TLR4 protein; Toll-like receptors; Transcriptomics; Tumors; Using RNA Sequencing and Profiling in Diagnosis and Treatment of Cancer
• ISSN: 1758-8359; 1758-8340; 1758-8359
• DOI: 10.1177/17588359231156382

Background: The current model of clinical drug development in oncology displays major limitations due to a high attrition rate in patient enrollment in early phase trials and a high failure rate of drugs in phase III studies. Objective: Integrating transcriptomics for selection of patients has the potential to achieve enhanced speed and efficacy of precision oncology trials for any targeted therapies or immunotherapies. Methods: Relative gene expression level in the metastasis and normal organ-matched tissues from the WINTHER database was used to estimate in silico the potential clinical benefit of specific treatments in a variety of metastatic solid tumors. Results: As example, high mRNA expression in tumor tissue compared to analogous normal tissue of c-MET and its ligand HGF correlated in silico with shorter overall survival (OS; p