对转移性透明细胞肾细胞癌免疫治疗耐药机制的研究。

IF 4.6 Q1 ONCOLOGY 癌症耐药(英文) Pub Date : 2023-01-01 DOI:10.20517/cdr.2023.09
Monica Sheila Chatwal, Jad Chahoud, Philippe E Spiess
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引用次数: 0

摘要

肾细胞癌(RCC)仍然是世界范围内癌症相关死亡的主要原因。尽管免疫检查点抑制剂和靶向治疗的新治疗组合大大改善了结果,但对这些疗法的耐药性正在成为长期控制的挑战。耐药机制已在多种实体肿瘤中被探索,包括肾细胞癌。基于我们对目前转移性透明细胞肾细胞癌(mccRCC)免疫治疗耐药机制的文献回顾,得出以下结论:随着检查点抑制剂和靶向口服治疗(单独和/或联合)的出现,mccRCC的治疗取得了实质性进展。然而,对这些疗法的先天或发展耐药性仍然是一个持续的挑战,特别是对免疫检查点抑制剂(ICIs)。一些已知的耐药机制已经得到了很好的定义,但最近细胞疗法的进展有助于扩大潜在的联合选择的范围,这些选择可能克服这些耐药模式,并改善长期的疾病控制和其他令人沮丧的疾病的生存。在随后的回顾和更新mccRCC免疫治疗耐药机制的文献中,我们重新审视了转移性透明细胞RCC免疫治疗的已知耐药机制,并探讨了目前和未来克服这些机制的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Revisiting mechanisms of resistance to immunotherapies in metastatic clear-cell renal-cell carcinoma.

Renal-cell carcinoma (RCC) remains a leading cause of cancer-related mortality worldwide. Though newer therapeutic combinations of immune checkpoint inhibitors and targeted therapies have greatly improved outcomes, resistance to these therapies is becoming a challenge for long-term control. Mechanisms of resistance have been explored in a variety of solid tumors, including RCC. Based upon our review of the current literature on the mechanisms of resistance to immunotherapies for the management of metastatic clear-cell renal cell carcinomas (mccRCC), the ensuing conclusions have been made: The management of mccRCC has progressed substantially with the advent of checkpoint inhibitors and targeted oral therapies, alone and/or in combination. Nevertheless, innate or developed resistance to these therapies remains an ongoing challenge, particularly to immune checkpoint inhibitors (ICIs). Several of the known mechanisms of resistance have been well defined, but recent progression in cellular therapies helps to expand the armamentarium of potential combination options that may overcome these modes of resistance and improve long-term disease control and survival for an otherwise dismal disease. In the ensuing review and update of the literature on the mechanisms of resistance to immunotherapies in mccRCC, we have revisited the known resistance mechanisms of immunotherapies in metastatic clear-cell RCC and explored ongoing and future strategies to overcome them.

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