DLL3在小细胞肺癌靶向治疗中的研究进展

Research Progress of DLL3 in Targeted Therapy of Small Cell Lung Cancer

小细胞肺癌(SCLC)是肺癌中恶性程度最高、侵袭性最强的亚型,广泛期SCLC患者对放化疗敏感,但是很快会产生耐药,并出现病情进展。Delta样配体3(DLL3)在大部分SCLC细胞中表达,而在正常组织中低表达甚至不表达,这一特点使DLL3特异性靶向SCLC细胞的疗法成为可能。靶向DLL3的抗体-药物偶联物Rova-T由于患者总生存期较短,其Ⅲ期试验已被停止,双特异性T细胞接合剂AMG 757和DLL3靶向的嵌合抗原受体T细胞AMG 119正在进行临床研究中,其余部分DLL3靶向疗法已完成临床前研究。未来,对DLL3靶向治疗方法进行深入探索有望为SCLC患者提供更有效的治疗选择。

Small cell lung cancer(SCLC)is the most malignant and aggressive subtype of lung cancer.Patients with extensive-stage SCLC are sensitive to radiotherapy and chemotherapy,but will soon be resistant and the disease will progress.Delta-like ligand 3(DLL3)is expressed in most SCLC tumor cells,but is low or not expressed in normal tissues,which makes it possible for DLL3 specifically targeted treatment for SCLC cells.DLL3-targeted antibody-drug conjugate Rovalpituzumab tesirine,has been suspended at phaseⅢtrial due to short overall survival time.Bispecific T cell engager AMG 757 and DLL3-targeted chimeric antigen receptor T cells AMG 119 are under clinical investigation,and the remaining DLL3-targeted therapies have completed preclinical studies.In the future,in-depth exploration of DLL3-targeted therapy is expected to provide more effective treatment options for SCLC patients.