Small-cell lung cancer (SCLC) is a recalcitrant form of cancer, representing 15% of lung cancer cases globally. SCLC is classified within the range of neuroendocrine pulmonary neoplasms, exhibiting shared morphologic, ultrastructural, immunohistochemical, and molecular genomic features. It is marked by rapid proliferation, a propensity for early metastasis, and an overall poor prognosis. The current conventional therapies involve platinum–etoposide-based chemotherapy in combination with immunotherapy. Nonetheless, the rapid emergence of therapeutic resistance continues to pose substantial difficulties. The genomic profiling of SCLC uncovers significant chromosomal rearrangements along with a considerable mutation burden, typically involving the functional inactivation of the tumor suppressor genes TP53 and RB1. Identifying biomarkers and evaluating new treatments is crucial for enhancing outcomes in patients with SCLC. Targeted therapies such as topoisomerase inhibitors, DLL3 inhibitors, HDAC inhibitors, PARP inhibitors, Chk1 inhibitors, etc., have introduced new therapeutic options for future applications. In this current review, we will attempt to outline the key molecular pathways that play a role in the development and progression of SCLC, together with a comprehensive overview of the most recent advancements in the development of novel targeted treatment strategies, as well as some ongoing clinical trials against SCLC, with the goal of improving patient outcomes.
小细胞肺癌（SCLC）是一种难治性癌症，约占全球肺癌病例的15%。它属于肺神经内分泌肿瘤范畴，具有共同的形态学、超微结构、免疫组织化学及分子基因组特征。该疾病以快速增殖、早期转移倾向和总体预后不良为特点。目前常规治疗主要采用铂类联合依托泊苷的化疗方案并结合免疫治疗。然而，治疗耐药性的快速出现仍构成重大挑战。SCLC的基因组分析揭示了显著的染色体重排及较高的突变负荷，通常涉及抑癌基因TP53和RB1的功能失活。识别生物标志物并评估新型疗法对于改善SCLC患者预后至关重要。拓扑异构酶抑制剂、DLL3抑制剂、HDAC抑制剂、PARP抑制剂、Chk1抑制剂等靶向治疗为未来应用提供了新的治疗选择。本综述旨在系统阐述参与SCLC发生发展的关键分子通路，全面概述新型靶向治疗策略的最新进展，并介绍部分正在进行的SCLC临床试验，以期为改善患者预后提供参考。
Recent Advances in the Clinical Translation of Small-Cell Lung Cancer Therapeutics
肿瘤(癌症)患者之家