随着对肾癌发病机制的日渐了解,小分子靶向药物如舒尼替尼和索拉非尼等已经被广泛应用于临床,显著提高了肾癌患者的生存时间。然而,约有15%的进展期肾癌患者对靶向药物先天耐药,其余患者在接受舒尼替尼治疗6~15个月后也往往出现耐药和疾病进展,成为晚期肾癌治疗的瓶颈。因此,探索肾癌靶向耐药的生物学机制以及寻找预测靶向药物疗效的生物学标记物十分迫切。我们团队近期的研究发现了在肾癌靶向药物耐药过程中起关键作用的长链非编码RNA(lncRNA),相关研究成果发表在Cancer Cell、Nature Communications和Oncogene等国际知名期刊上。本文总结了我们团队关于肾癌靶向药物耐药研究的新成果,并对未来靶向药物耐药研究的方向和难点进行了探讨。
Recently,improved comprehension of renal cell carcinoma(RCC)pathogenesis has led to the development of small molecule targeted-drug,receptor tyrosine kinase(RTK)inhibitors such as sunitinib and sorafenib,which are now the mainstay of therapeutic options for advanced RCC patients.However,15% of advanced RCC patients are inherently refractory to targeted-drug,and most of the remaining patients end up with drug resistance and tumor progression after 6-15 months of therapy with sunitinib,resulting in the failure to efficiently prolong the survival of RCC patients.Therefore,it is urgent to explore the potential mechanisms of targeted-drug resistance and to identify the biological markers to predict efficacy of targeted-drug in RCC.Recently,we found that long non-coding RNA(lncRNA)plays a key role in target-drug resistance of RCC,which had been published in Cancer Cell,Nature Communications and Oncogene.In this comment,we systematically reviewed our research results in targeted-drug resistance of RCC.Besides,we also share our views on future directions in targeted-drug resistance,hoping to provide implications for future study.