Morais Christudas
Centre for Kidney Disease Research, School of Medicine, The University of Queensland at Translational Research Institute, Brisbane, Queensland 4102, Australia.
J Kidney Cancer VHL. 2014 Apr 22;1(1):1-11. doi: 10.15586/jkcvhl.2014.7. eCollection 2014.
Of the many targeted therapies introduced since 2006, sunitinib has carved its way to become the most commonly used first-line therapy for the treatment of metastatic renal cell carcinoma (RCC). Despite significant improvements in progression-free survival, 30% of the patients are intrinsically resistant to sunitinib and the remaining 70% who respond initially will eventually become resistant in 6-15 months. While the molecular mechanisms of acquired resistance to sunitinib have been unravelling at a rapid rate, the mechanisms of intrinsic resistance remain elusive. Combination therapy, sunitinib rechallenge and sequential therapy have been investigated as means to overcome resistance to sunitinib. Of these, sequential therapy appears to be the most promising strategy. This mini review summarises our emerging understanding of the molecular mechanisms, and the strategies employed to overcome sunitinib resistance.
自2006年以来引入了多种靶向治疗药物，其中舒尼替尼已逐渐成为治疗转移性肾细胞癌（RCC）最常用的一线治疗药物。尽管无进展生存期有了显著改善，但30%的患者对舒尼替尼具有内在抗性，其余70%最初有反应的患者最终也会在6至15个月内产生抗性。虽然对舒尼替尼获得性抗性的分子机制已迅速得到揭示，但内在抗性的机制仍然难以捉摸。联合治疗、舒尼替尼再挑战和序贯治疗已作为克服对舒尼替尼抗性的手段进行了研究。其中，序贯治疗似乎是最有前景的策略。本综述总结了我们对分子机制以及克服舒尼替尼抗性所采用策略的新认识。
