Cancer Research UK London Research Institute, Translational Cancer Therapeutics Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
EPMA J. 2011 Dec 22;3(1):1. doi: 10.1007/s13167-011-0137-3.
Recent years have seen major advances in the management of metastatic renal cell carcinoma (mRCC). The tyrosine kinase and mammalian target of rapamycin inhibitors have resulted in disease control and improved survival for many patients with mRCC, but they have not led to preventive, predictive or personalised medicine (PPPM). Failure to achieve this rests ultimately with inadequate knowledge of tissue and molecular heterogeneity; discovery of these drugs was based upon identification of pathogenic molecular pathways in RCC, but research into molecular factors which underpin drug response, resistance and selection of therapy for individual patients has lagged well behind clinical trials of drug development. This review will provide an overview of the development of targeted drug therapies for mRCC, will discuss the challenges which currently impede the delivery of PPPM, including identification of biomarkers, drug resistance and molecular heterogeneity, and will propose research methodologies and technologies required to overcome these obstacles.
近年来，转移性肾细胞癌（mRCC）的治疗取得了重大进展。酪氨酸激酶和哺乳动物雷帕霉素靶蛋白抑制剂已经使许多 mRCC 患者的疾病得到控制并提高了生存率，但它们并没有导致预防性、预测性或个体化医学（PPPM）。未能实现这一目标最终归结于对组织和分子异质性的了解不足；这些药物的发现是基于对 RCC 中致病性分子途径的鉴定，但对支持药物反应、耐药性和为个体患者选择治疗的分子因素的研究远远落后于药物开发的临床试验。本文将概述 mRCC 靶向药物治疗的发展，讨论目前阻碍 PPPM 实施的挑战，包括生物标志物的鉴定、耐药性和分子异质性，并提出克服这些障碍所需的研究方法和技术。
