[Mechanisms and therapeutic strategies of small cell lung cancer transformation from non-small cell lung cancer after EGFR-TKIs treatment].

Lung cancer remains a leading cause of cancer-related mortality. In non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), histological transformation to small cell lung cancer (SCLC) can occur, leading to EGFR-TKI resistance. SCLC transformation not only challenges existing treatment strategies but also severely impacts patients prognosis. Here, we explore the underlying mechanisms of SCLC transformation, focusing on <i>RB1</i>/<i>TP53</i> genes, <i>MYC</i> gene, and the Notch and Wnt/β-catenin signaling pathways. We propose a hypothesis for SCLC transformation: co-mutation of <i>RB1</i>/<i>TP53</i> genes serves as a prerequisite, while combined abnormalities, such as aberrant <i>MYC</i> activation and dysregulated Notch or Wnt/β-catenin signaling, will further drive the transformation process. Currently, therapies for transformed SCLC are still exploratory. We discuss multimodal strategies, including chemotherapy, chemotherapy combined with EGFR-TKIs, chemotherapy combined with anti-angiogenic therapy, chemotherapy combined with immunotherapy, and radiotherapy. Finally, we outline future research directions. Future studies should unravel transformation mechanisms, conduct rigorous randomized trials, and develop precision interventions, paving new avenues for improved patient outcomes.​.