Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer.
Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer.
复制标题
靶向小细胞肺癌中δ样配体3（DLL3）的新兴疗法
DOI：
10.1186/s13045-023-01464-y
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发表时间：
2023-06-24
影响因子：
28.5
通讯作者：
Paz-Ares, Luis
中科院分区：
文献类型：
--
作者：
Rudin, Charles M. M.;Reck, Martin;Johnson, Melissa L. L.;Blackhall, Fiona;Hann, Christine L. L.;Yang, James Chih-Hsin;Bailis, Julie M. M.;Bebb, Gwyn;Goldrick, Amanda;Umejiego, John;Paz-Ares, Luis
关键词：
Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with a poor prognosis. Initial responses to standard-of-care chemo-immunotherapy are, unfortunately, followed by rapid disease recurrence in most patients. Current treatment options are limited, with no therapies specifically approved as third-line or beyond. Delta-like ligand 3 (DLL3), a Notch inhibitory ligand, is an attractive therapeutic target because it is overexpressed on the surface of SCLC cells with minimal to no expression on normal cells. Several DLL3-targeted therapies are being developed for the treatment of SCLC and other neuroendocrine carcinomas, including antibody-drug conjugates (ADCs), T-cell engager (TCE) molecules, and chimeric antigen receptor (CAR) therapies. First, we discuss the clinical experience with rovalpituzumab tesirine (Rova-T), a DLL3-targeting ADC, the development of which was halted due to a lack of efficacy in phase 3 studies, with a view to understanding the lessons that can be garnered for the rapidly evolving therapeutic landscape in SCLC. We then review preclinical and clinical data for several DLL3-targeting agents that are currently in development, including the TCE molecules—tarlatamab (formerly known as AMG 757), BI 764532, and HPN328—and the CAR T-cell therapy AMG 119. We conclude with a discussion of the future challenges and opportunities for DLL3-targeting therapies, including the utility of DLL3 as a biomarker for patient selection and disease progression, and the potential of rational combinatorial approaches that can enhance efficacy. The online version contains supplementary material available at 10.1186/s13045-023-01464-y.
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影响因子：
8.8
作者：
Borromeo MD;Savage TK;Kollipara RK;He M;Augustyn A;Osborne JK;Girard L;Minna JD;Gazdar AF;Cobb MH;Johnson JE
通讯作者：
Johnson JE
影响因子：
11.4
作者：
Duell, J.;Dittrich, M.;Topp, M. S.
通讯作者：
Topp, M. S.
影响因子：
51.1
作者：
Budde, Lihua E.;Sehn, Laurie H.;Bartlett, Nancy L.
通讯作者：
Bartlett, Nancy L.
影响因子：
5.7
作者：
Austin, Richard J.;Lemon, Bryan D.;Wesche, Holger
通讯作者：
Wesche, Holger
影响因子：
11.5
作者：
Deegen, Petra;Thomas, Oliver;Bailis, Julie M.
通讯作者：
Bailis, Julie M.