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嫌色细胞肾细胞癌:新出现的脆弱性为新的治疗格局带来希望

英文原题:Chromophobe renal cell carcinoma: Emerging vulnerabilities as a promise for a new therapeutic landscape.

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Chromophobe renal cell carcinoma: Emerging vulnerabilities as a promise for a new therapeutic landscape.

PubMed 2025/10/22(内容时间) Crit Rev Oncol Hematol Q1 · IF 6.2(JCR 2025)

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中文摘要

嫌色细胞肾细胞癌(ChRCC)是一种罕见肿瘤,也是第三常见的肾细胞癌亚型,其特征为低肿瘤突变负荷、线粒体异常以及独特的代谢依赖性。历史上,ChRCC被归入非透明细胞肾细胞癌,常被排除在组织学特异性试验之外,或被并入篮式试验,因此长期以来缺乏量身定制的治疗选择。近年来的努力已开始揭示其独特的生物学特征和治疗脆弱性。本综述总结了临床试验中涌现的数据,包括近期评估免疫检查点和酪氨酸激酶抑制剂的研究,并强调这些治疗在ChRCC中疗效不一。随后,我们基于ChRCC特异性特征描述了三条有前景的治疗途径:(1) 通过破坏谷胱甘肽稳态诱导铁死亡,(2) 靶向KIT的抗体-药物偶联物,以及(3) 自然杀伤过继细胞疗法。本综述强调需要持续的多专业协作,通过包容性和基于生物学的试验,将基础科学发现转化为ChRCC患者预后的改善。

展开英文摘要原文

Chromophobe renal cell carcinoma (ChRCC) is a rare tumor and the third most common subtype of renal cell carcinoma and is characterized by low tumor mutational burden, mitochondrial abnormalities, and distinct metabolic dependencies. Historically grouped under non-clear cell renal cell carcinoma and often excluded from histology-specific trials or lumped into basket trials, ChRCC has long lacked tailored therapeutic options.

Recent efforts have begun to bring to light its specific biology and therapeutic vulnerabilities. This review summarizes emerging data from clinical trials, including recent studies evaluating immune checkpoint and tyrosine kinase inhibitors, and highlights their variable efficacy in ChRCC.

We then describe three promising therapeutic avenues based on ChRCC-specific features: (1) ferroptosis induction through glutathione homeostasis disruption, (2) antibody-drug conjugates targeting KIT, and (3) natural killer adoptive cell therapy. This review underscores the need for continued multiprofessional collaboration to transform basic science discoveries into improved outcomes for ChRCC patients via inclusive and biology-informed trials.

论文信息

作者
Salem S、Alchoueiry M、Xu W、Henske EP
第一作者单位
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.United States
通讯作者单位
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: ehenske@bwh.harvard.edu.United States
文献类型
综述
期刊
Critical reviews in oncology/hematology2025 Dec
原文标识
PubMed 41135781 · DOI 10.1016/j.critrevonc.2025.104985