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小细胞肺癌 DLL3 靶向治疗的进展:挑战、机遇与未来方向

英文原题:Advances in DLL3-targeted therapies for small cell lung cancer: challenges, opportunities, and future directions.

PubMed 2024/12/05(内容时间) Front Oncol Q2 · IF 3.4(JCR 2025)

研究概要

小细胞肺癌(SCLC)仍是最具侵袭性、治疗最具挑战性的恶性肿瘤之一,治疗选择有限且结局较差。

中文摘要

小细胞肺癌(SCLC)仍是侵袭性最强、最难治疗的恶性肿瘤之一,治疗选择有限且预后不佳。近期对SCLC生物学的深入认识已将Delta样配体3(DLL3)确定为新型疗法的有前景靶点。本文综述SCLC中DLL3靶向治疗不断演变的格局,考察其作用机制、临床前研究前景和临床开发进展。讨论的治疗方式包括抗体药物偶联物(ADC)、双特异性T细胞衔接器(BiTE)、CAR-T 细胞疗法,以及近红外光免疫疗法(NIR-PIT)和放射性药物治疗(RPT)等新兴方法。本文指出了将这些有前景方法转化为临床实践时遇到的挑战,包括早期DLL3靶向疗法罗伐妥珠单抗替索林(Rova-T)遭遇的挫折。文章还探讨了克服这些障碍的潜在策略,强调需要更深入、细致地理解DLL3生物学及其在SCLC发病机制中的作用。整合前沿技术并加强跨学科合作,有望推动DLL3靶向疗法优化并改善SCLC患者结局。本综述全面介绍了DLL3靶向治疗的现状和未来方向,凸显其改变SCLC治疗格局的潜力。

展开英文摘要原文

Small cell lung cancer (SCLC) remains one of the most aggressive and challenging malignancies to treat, with limited therapeutic options and poor outcomes. Recent advances in understanding SCLC biology have identified Delta-like ligand 3 (DLL3) as a promising target for novel therapies. This review explores the evolving landscape of DLL3-targeted therapies in SCLC, examining their mechanistic basis, preclinical promise, and clinical development. We discuss various therapeutic modalities, including antibody-drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), chimeric antigen receptor T-cell (CAR-T) therapies, and emerging approaches such as near-infrared photoimmunotherapy (NIR-PIT) and radiopharmaceutical therapy (RPT). The review highlights the challenges encountered in translating these promising approaches into clinical practice, including the setbacks faced by early DLL3-targeted therapies like Rovalpituzumab Tesirine (Rova-T). We also explore potential strategies to overcome these obstacles, emphasizing the need for a more nuanced understanding of DLL3 biology and its role in SCLC pathogenesis. The integration of cutting-edge technologies and interdisciplinary collaboration is proposed as a path forward to optimize DLL3-targeted therapies and improve outcomes for SCLC patients. This comprehensive overview provides insights into the current state and future directions of DLL3-targeted therapies, underscoring their potential to revolutionize SCLC treatment paradigms.

论文信息

作者
Ding J、Yeong C
单位
Taylor's University, Subang Jaya, Selangor, Malaysia.Malaysia
文献类型
综述
期刊
Frontiers in oncology2024
原文标识
PubMed 39703856 · DOI 10.3389/fonc.2024.1504139