PTEN is a Potent Suppressor of Small Cell Lung Cancer
Mené à l'aide d'un modèle murin, cette étude met en évidence des mécanismes suggérant que le gène PTEN joue un rôle de suppresseur de tumeurs dans les cancers du poumon à petites cellules
Small cell lung carcinoma (SCLC) is a highly metastatic tumor type with neuroendocrine features and a dismal prognosis. PTEN mutations and PIK3CA activating mutations have been reported in SCLC but the functional relevance of this pathway is unknown. The PTEN/PIK3CA pathway was interrogated using an AdenoCre-driven mouse model of SCLC harboring inactivated Rb and p53. Inactivation of one allele of PTEN in Rb/p53-deleted mice led to accelerated SCLC with frequent metastasis to the liver. In contrast to the high mutation burden reported in human SCLC, exome analyses revealed a low number of protein-altering mutations in mouse SCLC. Inactivation of both alleles of PTEN in the Rb/p53-deleted system led to non-metastatic adenocarcinoma with neuroendocrine differentiation. This study reveals a critical role for the PTEN/PI3-kinase pathway in both SCLC and lung adenocarcinoma and provides an ideal system to test PI3-kinase pathway inhibitors as targeted therapy for subsets of SCLC patients. Implications: The ability of PTEN inactivation to accelerate SCLC in a genetic mouse model suggests that targeting the PTEN pathway is a therapeutic option for a subset of human SCLC patients.