Systemic Treatment for Advanced and Metastatic Non-Clear Cell Renal Cell Carcinoma: Examining Modern Therapeutic Strategies for a Notoriously Challenging Malignancy.
Systemic Treatment for Advanced and Metastatic Non-Clear Cell Renal Cell Carcinoma: Examining Modern Therapeutic Strategies for a Notoriously Challenging Malignancy.
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DOI：
10.15586/jkcvhl.v10i3.295
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发表时间：
2023
影响因子：
1.6
通讯作者：
中科院分区：
文献类型：
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非透明细胞肾细胞癌（nccRCC）是一组异质性恶性肿瘤，占肾细胞癌（RCC）病例的25%。非透明细胞组织学的治疗主要基于来自小型II期临床试验的证据或从透明细胞RCC的成功治疗中推断，因为非透明细胞病理学的发生率较低。基因组分析的进展提高了临床医生对nccRCC分子靶点的理解，例如改变的间充质上皮转化（MET）基因状态和富马酸水合酶（FH）基因失活，但患者结局仍然很差，这种疾病的最佳管理仍不清楚。本综述评估了27项前瞻性和13项正在进行的临床试验的组织学亚型的结果，以确定晚期或转移性nccRCC的治疗策略。血管内皮生长因子酪氨酸激酶抑制剂（TKI）（如舒尼替尼）和哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂（如依维莫司）已证明有效，并仍是可行的治疗选择，首选舒尼替尼。然而，依维莫司在嫌色细胞RCC患者中是优选的，因为滤泡素（FLCN）基因突变上调mTOR通路。新型TKI，如卡博替尼，由于靶向MET抑制，在乳头状RCC患者中显示出改善的结果。以铂为基础的化疗仍然是集合管和髓样肾细胞癌的推荐治疗策略。在所有非透明细胞组织学中观察到免疫检查点抑制剂（如nivolumab、pembrolizumab和ipilimumab）具有临床意义的抗肿瘤活性。正在进行的试验正在评估新的酪氨酸激酶抑制剂和免疫治疗联合方案，重点是有前途的MET抑制剂卡博替尼和派姆单抗加乐伐替尼。
Non-clear cell renal cell carcinoma (nccRCC) is a heterogeneous group of malignancies that represents 25% of renal cell carcinoma (RCC) cases. Treatment for non-clear cell histologies is mostly based on evidence from small phase II clinical trials or extrapolated from successful therapies in clear cell RCC because of the low incidence of non-clear cell pathology. Advances in genomic profiling have improved clinicians’ understanding of molecular targets for nccRCC, such as altered mesenchymal epithelial transition (MET) gene status and fumarate hydratase (FH) gene inactivation, but patient outcomes remain poor and optimal management of this disease remains unclear. This review assesses outcomes by histologic subtype from 27 prospective and 13 ongoing clinical trials to identify therapeutic strategies for advanced or metastatic nccRCC. Vascular endothelial growth factor tyrosine kinase inhibitors (TKI), such as sunitinib, and mammalian target of rapamycin (mTOR) inhibitors, such as everolimus, have demonstrated efficacy and remain viable treatment options, with a preference for sunitinib. However, everolimus is preferred in patients with chromophobe RCC because folliculin (FLCN) gene mutations upregulate the mTOR pathway. Novel TKIs, such as cabozantinib, show improved outcomes in patients with papillary RCC because of targeted MET inhibition. Platinum-based chemotherapy continues to be the recommended treatment strategy for collecting duct and medullary RCC. Clinically meaningful antitumor activity has been observed across all non-clear cell histologies for immune checkpoint inhibitors, such as nivolumab, pembrolizumab, and ipilimumab. Ongoing trials are evaluating novel tyrosine kinase inhibitor and immunotherapy combination regimens, with an emphasis on the promising MET-inhibitor cabozantinib and pembrolizumab plus lenvatinib.
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影响因子：
64.8
作者：
Bertolotto, Corine;Lesueur, Fabienne;Bressac-de Paillerets, Brigitte
通讯作者：
Bressac-de Paillerets, Brigitte
影响因子：
45.3
作者：
Choueiri, Toni K.;Vaishampayan, Ulka;Srinivasan, Ramaprasad
通讯作者：
Srinivasan, Ramaprasad
影响因子：
5.6
作者：
Chevarie-Davis, Myriam;Riazalhosseini, Yasser;Brimo, Fadi
通讯作者：
Brimo, Fadi
影响因子：
8.4
作者：
Escudier, Bernard;Molinie, Vincent;Albiges, Laurence
通讯作者：
Albiges, Laurence
影响因子：
9.3
作者：
Bertrand A;Kostine M;Barnetche T;Truchetet ME;Schaeverbeke T
通讯作者：
Schaeverbeke T