Transformation Into Small Cell Lung Cancer : a Mode of Resistance to Treatment

The discovery of oncogenic mutations and the use of targeted therapies have transformed the management of certain tumors. Thus 12 to 15% of bronchial adenocarcinomas (AD) carry mutations of EGFR and receive from the first line inhibitors of this kinase (ITK). Despite spectacular results, relapse and resistance are quasi-general phenomena. In most known cases, EGFR-TKI resistance mechanisms involve secondary mutations of EGFR or the activation of alternative oncogenic pathways. However, in 5 to 15% of patients, resistance is manifested by the emergence of a small cell carcinoma (CPC), a cancer of neuroendocrine origin very different from AD by its cellular, molecular and epidemiological characteristics. This phenotypic transformation is an almost unique phenomenon in oncology and its molecular bases are not understood. To study this phenomenon, a Franco-Italian network was established that documented and collected cases of this rare tumor. This series is the subject of detailed anatomopathological, clinical and therapeutic documentation. This project aims to investigate the exome of one or more matched lesion regions to evaluate the evolutionary processes leading from the initial AD to the relapsing CPC. These results will guide future research on predictive markers of relapse and their targeted treatment.