Jain Aayushi, Jahagirdar Devashree, Nilendu Pritish, Sharma Nilesh Kumar
a Cancer and Translational Research Lab , Dr. D.Y. Patil Biotechnology & Bioinformatics Institute , Pune , India.
Expert Rev Anticancer Ther. 2017 Sep;17(9):815-825. doi: 10.1080/14737140.2017.1356231. Epub 2017 Jul 20.
Cisplatin has been considered as the crucial regimen of widely prescribed chemotherapy treatment for cancer. The advancing treatment of cancers has reached the border line, where tumors show resistance to cisplatin and may thwart its use. Other than issues of drug resistance, cisplatin has been reported to evince side effects such as nephrotoxicity and ototoxicity. Therefore, there is a compelling need to untangle the problems associated with cisplatin treatment in carcinoma. Areas covered: In this review, we summarize the current status of combinatorial options to bring about better pre-clinical and clinical cisplatin drug responses in carcinoma. We begin with problems associated with cisplatin drugs and current avenues such as depicting molecular modulation of enhanced influx and reduced efflux. We also discuss the scope of the DNA damage response landscape and contribution of regulatory small RNAs towards potentiation of cisplatin responses. Expert commentary: The extensive use of cisplatin and incessant high drug dose have prompted the scientific community to limit the burden of cisplatin without compromising therapeutic success. Currently, there are reports on the potential use of other non-toxic small molecule inhibitors, interference RNAs and peptide mimetics to get rid of cellular adversities responsible for cisplatin resistance and high dose effects.
顺铂一直被视为癌症广泛使用的化疗治疗的关键方案。癌症治疗的进展已达到临界线,此时肿瘤对顺铂产生耐药性,可能阻碍其使用。除了耐药性问题外,据报道顺铂还会引发肾毒性和耳毒性等副作用。因此,迫切需要解决与顺铂治疗癌症相关的问题。涵盖领域:在本综述中,我们总结了组合方案的现状,以在癌症中实现更好的临床前和临床顺铂药物反应。我们从与顺铂药物相关的问题以及当前途径开始,例如描述增强内流和减少外流的分子调节。我们还讨论了DNA损伤反应格局的范围以及调节性小RNA对增强顺铂反应的贡献。专家评论:顺铂的广泛使用和持续的高药物剂量促使科学界在不影响治疗成功的情况下减轻顺铂的负担。目前,有报道称其他无毒小分子抑制剂、干扰RNA和肽模拟物有潜在用途,以消除导致顺铂耐药性和高剂量效应的细胞逆境。