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小细胞肺癌免疫治疗新靶点的研究进展。

Advances in new targets for immunotherapy of small cell lung cancer.

机构信息

Department of Oncology, Binzhou Medical University Hospital, Binzhou, P.R. China.

Center of Biotherapy, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China.

出版信息

Thorac Cancer. 2024 Jan;15(1):3-14. doi: 10.1111/1759-7714.15178. Epub 2023 Dec 13.


DOI:10.1111/1759-7714.15178
PMID:38093497
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10761621/
Abstract

Small cell lung cancer (SCLC) is one of the highly aggressive malignancies characterized by rapid growth and early metastasis, but treatment options are limited. For SCLC, carboplatin or cisplatin in combination with etoposide chemotherapy has been considered the only standard of care, but the standard first-line treatment only results in 10-month survival. The majority of patients relapse within a few weeks to months after treatment, despite the relatively sensitive response to chemotherapy. Over the past decade, immunotherapy has made significant progress in the treatment of SCLC patients. However, there have been limited improvements in survival rates for SCLC patients with the current immune checkpoint inhibitors PD-1/PD-L1 and CTLA-4. In the face of high recurrence rates, small beneficiary populations, and low survival benefits, the exploration of new targets for key molecules and signals in SCLC and the development of drugs with novel mechanisms may provide fresh hope for immunotherapy in SCLC. Therefore, the aim of this review was to explore four new targets, DLL3, TIGIT, LAG-3, and GD2, which may play a role in the immunotherapy of SCLC to find useful clues and strategies to improve the outcome for SCLC patients.

摘要

小细胞肺癌(SCLC)是一种高度侵袭性的恶性肿瘤,其特点是生长迅速、早期转移,但治疗选择有限。对于 SCLC,卡铂或顺铂联合依托泊苷化疗被认为是唯一的标准治疗方法,但标准一线治疗仅导致 10 个月的生存。大多数患者在治疗后数周到数月内复发,尽管对化疗有相对敏感的反应。在过去的十年中,免疫疗法在 SCLC 患者的治疗中取得了重大进展。然而,目前的免疫检查点抑制剂 PD-1/PD-L1 和 CTLA-4 对 SCLC 患者的生存率提高有限。面对高复发率、受益人群小和生存获益低的情况,探索 SCLC 中关键分子和信号的新靶点以及开发具有新机制的药物可能为 SCLC 的免疫疗法提供新的希望。因此,本综述旨在探讨四个新的靶点,即 DLL3、TIGIT、LAG-3 和 GD2,它们可能在 SCLC 的免疫治疗中发挥作用,以寻找改善 SCLC 患者预后的有用线索和策略。

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[1]
Immunotherapy of small cell lung cancer based on prognostic nutritional index.

Front Immunol. 2025-5-26

[2]
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Curr Oncol. 2025-4-30

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Am J Cancer Res. 2025-3-15

[6]
Immunotherapy for small cell lung cancer: the current state and future trajectories.

Discov Oncol. 2024-8-16

本文引用的文献

[1]
Molecular subtypes, predictive markers and prognosis in small-cell lung carcinoma.

J Clin Pathol. 2024-12-18

[2]
C-Myc-induced hypersialylation of small cell lung cancer facilitates pro-tumoral phenotypes of macrophages.

iScience. 2023-8-29

[3]
Metabolic challenges and interventions in CAR T cell therapy.

Sci Immunol. 2023-4-14

[4]
Tarlatamab, a First-in-Class DLL3-Targeted Bispecific T-Cell Engager, in Recurrent Small-Cell Lung Cancer: An Open-Label, Phase I Study.

J Clin Oncol. 2023-6-1

[5]
Targeting the Notch signaling pathway and the Notch ligand, DLL3, in small cell lung cancer.

Biomed Pharmacother. 2023-3

[6]
Considerations for design, manufacture, and delivery for effective and safe T-cell engager therapies.

Curr Opin Biotechnol. 2022-12

[7]
Emerging Biomarkers and the Changing Landscape of Small Cell Lung Cancer.

Cancers (Basel). 2022-8-3

[8]
Phase I trial of the DLL3/CD3 bispecific T-cell engager BI 764532 in DLL3-positive small-cell lung cancer and neuroendocrine carcinomas.

Future Oncol. 2022-8

[9]
Randomized phase 3 study of the anti-disialoganglioside antibody dinutuximab and irinotecan vs irinotecan or topotecan for second-line treatment of small cell lung cancer.

Lung Cancer. 2022-4

[10]
CAR NK-92 cells targeting DLL3 kill effectively small cell lung cancer cells in vitro and in vivo.

J Leukoc Biol. 2022-10

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