Non–clear cell renal cell carcinoma (nccRCC) accounts for approximately 25% of RCC diagnoses. Although broadly labeled as “nccRCC,” they comprised a host of histologies that include papillary, chromophobe, unclassified, and others. Moreover, these histological variants are further subclassified on the basis of genomic profiling, thereby highlighting nccRCC to be anything but a homogenous cohort of RCC. The heterogeneity of nccRCC has proved challenging in developing therapeutics for this population. Although ccRCC therapeutic data have been commonly extrapolated for the treatment of nccRCC, the overall poor outcome of these patients highlights an unmet need. In an era of precision medicine, genomic analysis, and predictive biomarkers, novel approach to drug design and development is necessary to optimize treatment outcomes in nccRCC patients. Herein, we provide an overview of the nccRCC histologies, clinical trial data, and future opportunities for treatment options and development in nccRCC.

非透明细胞肾细胞癌(nccRCC) 约占 RCC 诊断的 25%。尽管广泛标记为“nccRCC”，但它们包含许多组织学，包括乳头状、嫌色细胞、未分类等。此外，这些组织学变异在基因组分析的基础上进一步细分，从而突出了 nccRCC 绝不是 RCC 的同质队列。nccRCC 的异质性已证明在为该人群开发治疗方法方面具有挑战性。尽管 ccRCC 治疗数据通常被外推用于 nccRCC 的治疗，但这些患者的总体不良结果凸显了未满足的需求。在精准医学、基因组分析和预测性生物标志物的时代，需要新的药物设计和开发方法来优化 nccRCC 患者的治疗结果。在此，我们概述了 nccRCC 的组织学、临床试验数据以及 nccRCC 治疗选择和发展的未来机会。