The emerging landscape and future perspective of SCLC transformation: From molecular mechanisms to therapeutic strategies

Small-cell lung cancer (SCLC) is featured by high malignancy and undesirable prognosis. Transformed SCLC shares several common grounds but differ in biological behavior, molecular mechanism and therapeutic options from typical SCLC. SCLC transformation exerts indispensable role in drug resistance among patients with non-small cell lung cancer (NSCLC) upon various treatment modalities. Two hypotheses have been raised to account for SCLC transformation. It develops mostly in EGFR-mutant adenocarcinoma, and can also occur in ALK or ROS1 mutant patients, and EGFR-wildtype adenocarcinoma. Effective biomarkers for early detection, and therapeutic strategies are vital for improving survival for patients undergoing SCLC transformation. This review summarizes the emerging landscape in transformed SCLC, including its origin, molecular mechanisms, approaches for early detection and corresponding therapeutic options, in a bid to gain a comprehensive insight of this recalcitrant and tricky disease. More importantly, we also discuss challenges that lie ahead and future perspectives on this aggressive malignancy.