Oncogenèse pulmonaire et bases biologiques des traitements ciblés

Abstract

Lung carcinogenesis results from a multi-step process involving the accumulation of several molecular abnormalities linked, in smokers, to the interaction between the DNA of the epithelial cells of the respiratory system and the carcinogens of tobacco smoke. In non-smokers, the number of molecular abnormalities is lower, but it is the acquisition of a main molecular alteration (mutation or translocation) that makes the cell dependent for its survival on this alteration, either an “oncogenic addiction”. This main anomaly is most often a so-called “driver” mutation, activating an oncogene, a gene whose product promotes uncontrolled proliferation of the tumor cell. Patients with lung cancer harboring an oncogenic driver may be eligible for treatments specifically targeting this driver, treatments which have considerably improved their survival. However, when subjected to such treatments, tumor cells inevitably end up developing resistance mechanisms, which must then be identified in order to be able to adapt the therapeutic management of patients. This review of the literature aims to recall the main mechanisms of pulmonary carcinogenesis in order to understand what today constitutes the basis of the targeted treatments offered to patients with lung cancer according to the molecular abnormalities of their tumor, but also to understand why, these tumors will find a way to resist these targeted treatments and what strategies must be put in place to monitor the evolution of both the patient and his tumor, and adapt their therapeutic care in response to these changes.1877-1203/© 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.