Solid Tumor Oncology (GU & GI), Medical Oncology Service, University Hospital del Mar-IMIM, Barcelona, Spain.
St Luke's-Roosevelt Hospital Center, Beth Israel Medical Center, Continuum Cancer Centers, New York, USA.
Ann Oncol. 2013 Jul;24(7):1730-1740. doi: 10.1093/annonc/mdt152. Epub 2013 Apr 26.
Targeted therapies have shown profound effects on the outcome of patients with advanced renal cell carcinoma (RCC). However, the optimal treatment for RCC of non-clear cell histology (nccRCC)-typically excluded from trials of targeted agents-remains uncertain.
By carrying out extensive searches of PubMed and ASCO databases, we identified and summarised research into the biological characteristics, clinical behaviour and treatment of different histological subtypes of nccRCC, focusing on targeted therapy.
The available data suggest that treatments currently approved for RCC are active in ncc subtypes, although the overall clinical benefit may be less than for clear cell RCC. Temsirolimus has proven benefit over interferon-alfa (IFN-α) in patients with nccRCC, based on phase III data, while everolimus, sunitinib and sorafenib have all demonstrated some degree of activity in nccRCC in expanded-access trials. No clear picture has emerged of whether individual histological subtypes are particularly responsive to any individual treatment.
Further molecular studies into the pathogenesis of RCC histological subtypes will help direct the development of novel, appropriate targeted agents. Clinical trials specifically designed to evaluate the role of targeted agents in nccRCC are ongoing, and data from trials with sunitinib and everolimus will be reported soon.
靶向治疗对晚期肾细胞癌（RCC）患者的预后产生了深远的影响。然而，对于非透明细胞组织学（nccRCC）的 RCC 的最佳治疗方法仍然不确定，nccRCC 通常被排除在靶向药物试验之外。
通过对 PubMed 和 ASCO 数据库进行广泛搜索，我们确定并总结了针对不同 nccRCC 组织学亚型的生物学特征、临床行为和治疗的研究，重点是靶向治疗。
现有数据表明，目前批准用于 RCC 的治疗方法对 ncc 亚型有效，尽管总体临床获益可能低于透明细胞 RCC。基于 III 期数据，替西罗莫司在 nccRCC 患者中优于干扰素-α（IFN-α），而依维莫司、舒尼替尼和索拉非尼在扩大准入试验中均显示出对 nccRCC 的一定程度的活性。对于特定的治疗方法是否对特定的组织学亚型特别有效，还没有明确的结论。
对 RCC 组织学亚型发病机制的进一步分子研究将有助于指导新型、合适的靶向药物的开发。专门设计用于评估靶向药物在 nccRCC 中的作用的临床试验正在进行中，舒尼替尼和依维莫司试验的数据将很快公布。
