Arquivos de Oncologia Cirúrgica

MATCH-R, Development of preclinical models from patients with acquired resistance to targeted therapy

Abstract

Ludovic Bigot

Advances in molecular oncology and cancer genetics in the last 15 years have defined many of the key driving oncogenes in human cancer. Despite these successes it is now apparent that tumor cells adapt and develop acquired resistance to these targeted inhibitors so that disease progresses within a 5-7 months. At Gustave Roussy, we have opened a prospective clinical trial, MATCH-R (NCT02517892): is a prospective single-institution trial aiming to identify mechanisms of resistance to targeted agents and immunotherapy in patients with advanced cancer (NCT02517892). Patients was enrolled to MATCH-R study before initiated a therapy and then they achieved an initial partial or complete response or stability of disease for at least 6 months are included upon disease progression. Extensive molecular profiling with panel next-generation sequencing, whole exome sequencing (WES) and RNA sequencing (RNAseq) is performed on tumor samples. In the same time, we develop preclinical models (Patient derived xenograft, organoids, and Notes: cell lines) at the stage of acquired resistance. These models will be used to improve our knowledge on the mechanisms underlying resistance to treatment and to develop new therapeutic strategy set up for the patient. As November 2019, 200 tumor biopsies were taken from patients to develop 70 PDX models, 20 organoids and 30 cell lines to develop preclinical research at Gustave Roussy. We carry our efforts on androgen therapy for prostate cancer, ALK/EGFR inhibitor for lung cancer and FGFR inhibitors for bladder and cholangiocarcinoma.