Small Cell Lung Cancer Signaling

Small cell lung carcinoma (SCLC) is a highly aggressive neoplasm with a high metastatic potential and the development of resistance to chemotherapy. It accounts for approximately 20% of all lung cancer cases. Altered expression of oncogenic and tumor suppressor genes play an important role in SCLC. For example, dominant oncogenes of the MYC family are frequently overexpressed in SCLC. Such overexpression leads to rapid cellular proliferation and loss of terminal differentiation. Mutations or deletions to tumor supressor genes like PTEN, RB and p53 interfere with cellular processes resulting in reduced apoptosis, increased proliferation and impaired cell cycle arrest thus contributing to the progression of the tumor.Other mutants include FHIT, a diadenosine triphosphate hydrolase which is thought to have an indirect role in proapoptosis and cell-cycle control. ECM and Bcl-2 protect SCLC cells against chemotherapy-induced cell death thus contributing to the disease.Retinoic acid plays an important role in lung development and differentiation acting primarily via nuclear receptors encoded by the retinoic acid receptor (RAR)-β gene. Promoter methylation and silencing of the RARβ gene is frequently seen in SCLC.