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小细胞肺癌:精准治疗的新兴靶点与策略

英文原题:Small Cell Lung Cancer: Emerging Targets and Strategies for Precision Therapy.

查看英文原题

Small Cell Lung Cancer: Emerging Targets and Strategies for Precision Therapy.

PubMed 2023/08/08(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

小细胞肺癌(SCLC)是一种侵袭性肺癌亚型,治疗选择有限。精准医学已改变多种肿瘤的治疗,但由于缺乏可靶向生物标志物,SCLC 的进展较慢。本综述概述 SCLC 精准治疗的新兴策略,包括靶向激酶抑制剂、单克隆抗体、血管生成抑制剂、抗体药物偶联物、PARP 抑制剂及表观遗传调节剂。血管生成抑制剂和 PARP、ATR 抑制剂等 DNA 损伤药物已在 SCLC 中进行探索,但迄今疗效有限,相关试验仍在进行。通过抗体药物偶联物、双特异性 T 细胞衔接器和 CAR-T 细胞疗法靶向 NOTCH 配体 DLL3,为未来治疗开辟了新选择。

此外,研究者还在探索表观遗传疗法逆转转录抑制、调节抗肿瘤免疫,以及利用抗体药物偶联物靶向 SCLC 细胞表面特异性靶点。尽管 SCLC 精准治疗进展面临挑战,近期进展仍为改善治疗结局带来希望。但仍需解决若干问题,包括药物耐药和肿瘤异质性。还需要进一步研究及生物标志物筛选的临床试验,以开发有效的 SCLC 精准疗法。

展开英文摘要原文

Small cell lung cancer is an aggressive subtype of lung cancer with limited treatment options. Precision medicine has revolutionized cancer treatment for many tumor types but progress in SCLC has been slower due to the lack of targetable biomarkers. This review article provides an overview of emerging strategies for precision therapy in SCLC. Targeted therapies include targeted kinase inhibitors, monoclonal antibodies, angiogenesis inhibitors, antibody-drug conjugates, PARP inhibitors, and epigenetic modulators.

Angiogenesis inhibitors and DNA-damaging agents, such as PARP and ATR inhibitors, have been explored in SCLC with limited success to date although trials are ongoing. The potential of targeting DLL3, a NOTCH ligand, through antibody-drug conjugates, bispecific T-cell engagers, and CAR T-cell therapy, has opened up new therapeutic options moving forward.

Additionally, new research in epigenetic therapeutics in reversing transcriptional repression, modulating anti-tumor immunity, and utilizing antibody-drug conjugates to target cell surface-specific targets in SCLC are also being investigated. While progress in precision therapy for SCLC has been challenging, recent advancements provide optimism for improved treatment outcomes.

However, several challenges remain and will need to be addressed, including drug resistance and tumor heterogeneity.

Further research and biomarker-selected clinical trials are necessary to develop effective precision therapies for SCLC patients.

论文信息

作者
Patel SR、Das M
单位
Department of Medicine, Division of Medical Oncology, Stanford Cancer Institute, Stanford University, Palo Alto, CA 94305, USA.United States
文献类型
综述
期刊
Cancers2023 Aug 8
原文标识
PubMed 37627044 · DOI 10.3390/cancers15164016