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Abstract：
Clear cell renal cell carcinoma (ccRCC) treatment has undergone three major paradigm shifts in recent years, first with the introduction of molecular targeted therapies, then with immune checkpoint inhibitors, and, more recently, with immune-based combinations. However, to date, molecular predictors of response to targeted agents have not been identified for ccRCC. The WHO 2022 classification of renal neoplasms introduced the molecularly defined RCC class, which is a first step in the direction of a better molecular profiling of RCC. We reviewed the literature data on known genomic alterations of clinical interest in ccRCC, discussing their prognostic and predictive role. In particular, we explored the role of VHL, mTOR, chromatin modulators, DNA repair genes, cyclin-dependent kinases, and tumor mutation burden. RCC is a tumor whose pivotal genomic alterations have pleiotropic effects, and the interplay of these effects determines the tumor phenotype and its clinical behavior. Therefore, it is difficult to find a single genomic predictive factor, but it is more likely to identify a signature of gene alterations that could impact prognosis and response to specific treatment. To accomplish this task, the interpolation of large amounts of clinical and genomic data is needed. Nevertheless, genomic profiling has the potential to change real-world clinical practice settings.
摘要：
肾透明细胞癌(ccRCC)治疗近年来经历了三大范式转变,首先是分子靶向治疗的引入，然后用免疫检查点抑制剂，and,最近,基于免疫的组合。然而,到目前为止,尚未确定ccRCC对靶向药物反应的分子预测因子。肾肿瘤的WHO2022分类引入了分子定义的RCC类别，这是朝着更好的RCC分子谱分析方向迈出的第一步。我们回顾了ccRCC临床感兴趣的已知基因组改变的文献数据，讨论它们的预后和预测作用。特别是,我们探讨了VHL的作用，mTOR,染色质调节剂,DNA修复基因,细胞周期蛋白依赖性激酶，和肿瘤突变负担。RCC是一种肿瘤，其关键的基因组改变具有多效性作用，这些效应的相互作用决定了肿瘤的表型和临床行为。因此,很难找到一个单一的基因组预测因子，但更有可能鉴定出可能影响预后和对特定治疗反应的基因改变的特征。为了完成这项任务,需要对大量临床和基因组数据进行插值。然而，基因组分析有可能改变现实世界的临床实践设置.
