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BRAF 突变黑色素瘤个体化治疗的进展与挑战:综合综述

英文原题:Advancements and Challenges in Personalized Therapy for BRAF-Mutant Melanoma: A Comprehensive Review.

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Advancements and Challenges in Personalized Therapy for BRAF-Mutant Melanoma: A Comprehensive Review.

PubMed 2024/09/12(内容时间) J Clin Med Q1 · IF 3.3(JCR 2025)

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中文摘要

在过去的几十年里,BRAF突变黑色素瘤治疗的进展促进了BRAF抑制剂、BRAF/MEK抑制剂联合治疗、抗PD-1治疗和抗CTLA4治疗的发展。尽管这些疗法在临床试验中显示出显著疗效,但其持续有效性常常受到肿瘤微环境的挑战,肿瘤微环境是一个高度异质且复杂的免疫抑制细胞环境,影响肿瘤进展。个性化医疗时代为根据个体遗传特征定制治疗带来了巨大希望。然而,肿瘤异质性和免疫逃逸机制导致了对免疫治疗的耐药性。尽管存在这些挑战,以lifileucel为代表的TIL(肿瘤浸润淋巴细胞)疗法已显示出对BRAF V600突变黑色素瘤的显著疗效。此外,早期反应生物标志物,如COX-2和MMP2,以及FDG-PET成像,为通过预测患者反应和确定最佳治疗持续时间来改善个性化免疫治疗提供了潜力。未来的努力应集中于缩短T细胞采集周期和降低TIL疗法的相关成本,以提高效率和可及性。

展开英文摘要原文

Over the past several decades, advancements in the treatment of BRAF -mutant melanoma have led to the development of BRAF inhibitors, BRAF /MEK inhibitor combinations, anti-PD-1 therapy, and anti-CTLA4 therapy.

Although these therapies have shown substantial efficacy in clinical trials, their sustained effectiveness is often challenged by the tumor microenvironment, which is a highly heterogeneous and complex milieu of immunosuppressive cells that affect tumor progression. The era of personalized medicine holds substantial promise for the tailoring of treatments to individual genetic profiles.

However, tumor heterogeneity and immune evasion mechanisms contribute to the resistance to immunotherapy. Despite these challenges, tumor-infiltrating lymphocyte (TIL) therapy, as exemplified by lifileucel, has demonstrated notable efficacy against BRAF V600 -mutant melanoma.

Additionally, early response biomarkers, such as COX-2 and MMP2, along with FDG-PET imaging, offer the potential to improve personalized immunotherapy by predicting patient responses and determining the optimal treatment duration. Future efforts should focus on reducing the T-cell harvesting periods and costs associated with TIL therapy to enhance efficiency and accessibility.

论文信息

作者
Shebrain A、Idris OA、Jawad A、Zhang T、Xing Y
第一作者单位
Department of Biological Sciences, Western Michigan University, Kalamazoo, MI 49008, USA.United States
通讯作者单位
Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA 91010, USA.United States
文献类型
综述
期刊
Journal of clinical medicine2024 Sep 12
原文标识
PubMed 39336897 · DOI 10.3390/jcm13185409