Mari Andrea, D'Andrea David, Abufaraj Mohammad, Foerster Beat, Kimura Shoji, Shariat Shahrokh F
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan.
Transl Androl Urol. 2017 Dec;6(6):1081-1089. doi: 10.21037/tau.2017.08.19.
Bladder cancer (BCa) is burdened by high rates of chemo- and radio-resistance. We reviewed and summarized the current evidence regarding the genetic determinants of resistance in patients treated with chemotherapy and/or radiotherapy (RT) for BCa. Genetic heterogeneity may preexist to treatment arising with tumorigenesis or increasing progressively during the treatment. Several biological pathways seem to be involved in the cellular response to treatment. These pathways comprehend mechanisms leading to modify the intracellular concentration of the drug, mechanisms leading to increase the repair of DNA damage caused by the treatment, mechanisms leading to increase cell survival, despite DNA damage, acting on the signaling pathways affecting apoptosis, mechanisms promoting autophagy. In the present review, we focused on the genetic determinants of resistance affecting the aforementioned mechanisms.
膀胱癌(BCa)面临着高化疗和放疗耐药率的负担。我们回顾并总结了目前关于接受化疗和/或放疗(RT)治疗的BCa患者耐药性遗传决定因素的证据。遗传异质性可能在肿瘤发生时就已存在于治疗前,或者在治疗过程中逐渐增加。几种生物学途径似乎参与了细胞对治疗的反应。这些途径包括导致改变药物细胞内浓度的机制、导致增加对治疗引起的DNA损伤修复的机制、导致增加细胞存活的机制(尽管存在DNA损伤,作用于影响细胞凋亡的信号通路)、促进自噬的机制。在本综述中,我们重点关注影响上述机制的耐药性遗传决定因素。