Rasmussen Neal, Rathmell W Kimryn
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Curr Clin Pharmacol. 2011 Aug;6(3):199-206. doi: 10.2174/157488411797189389.
The incidence rates of renal cell carcinoma (RCC) have continued to rise with 58,000 new cases in the United States. RCC has notoriously been refractory to traditional chemotherapeutic including radiation and cytokine therapies. The advent of the use of molecularly targeted therapies for RCC has significantly improved the standard of care. Yet, there still remains room for improvement as many of the current therapies are limited by acquired resistance and dosing restrictions due to toxicity. In this review we discuss many potential therapeutic targets that have been suggested for development as advancements are made in discovering the underlying molecular biology of RCC. Among the targets that discussed are additional targets within the well-established VHL/HIF axis, the PI3K/AKT/mTOR pathway, independent targets, and those identified by synthetic lethality screens.
在美国，肾细胞癌（RCC）的发病率持续上升，每年新增病例达58000例。众所周知，RCC对包括放疗和细胞因子疗法在内的传统化疗具有耐药性。分子靶向疗法在RCC治疗中的应用显著提高了治疗标准。然而，由于目前许多疗法受到获得性耐药和毒性导致的剂量限制，仍有改进空间。在本综述中，随着在发现RCC潜在分子生物学方面取得进展，我们讨论了许多已被建议用于开发的潜在治疗靶点。所讨论的靶点包括成熟的VHL/HIF轴内的其他靶点、PI3K/AKT/mTOR通路、独立靶点以及通过合成致死筛选确定的靶点。
