Advances and future perspectives in the treatment of small cell lung cancer: From chemotherapy and radiotherapy to the era of targeted therapy and immunotherapy.

Abstract

ABSTRACT Small cell lung cancer (SCLC) is an aggressive malignant tumor that mainly originates from pulmonary neuroendocrine cells and is characterized by rapid proliferation, high metastatic potential, and acquired therapeutic resistance. The therapeutic landscape for SCLC is largely confined to traditional modalities, such as surgery and chemoradiotherapy. However, 80-85% of patients are diagnosed with extensive-stage SCLC at initial presentation; surgical intervention and radiotherapy are often not applicable for these patients. Despite the initial favorable response of SCLC to chemotherapy, most patients develop resistance and experience rapid disease recurrence, leading to a poor prognosis. Historically, radiotherapy was the main mode of first-line treatment. With the advent of immune checkpoint inhibitors (ICIs) in recent years, the field of oncology has witnessed new therapeutic modalities and strategies. The combination of immunotherapy and chemotherapy has led to the development of extremely effective strategies for treating SCLC, significantly extending overall survival for a subset of patients. However, the overall clinical benefit remains limited; therefore, further optimization needs to be performed. This need has encouraged researchers to investigate novel therapeutic strategies. Antibody-drug conjugates targeting antigens, such as DLL3, B7-H3, and TROP2, are extremely effective in treating relapsed/refractory SCLC. In this review, the latest research advances in the carcinogenic, invasive, and drug-resistance mechanisms of SCLC have been summarized. We focused on the progress in the treatment modalities for SCLC and discussed future perspectives involving novel therapeutic combinations, assessment of new targets, and strategies to overcome treatment resistance.