Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment.

Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment.
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靶向DNA损伤反应和修复以提高基于顺铂的癌症治疗的治疗指数。

DOI:
10.3390/ijms22158199
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发表时间:
2021-07-30
影响因子:
5.6
通讯作者:
Acklin S
Acklin S
中科院分区:
生物学2区
文献类型:
--
作者:
Kiss RC;Xia F;Acklin S

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铂类化疗,例如顺铂,在癌症治疗中发挥着重要作用。然而,耐药性和治疗毒性的发展给疾病控制造成了巨大障碍。为了提高顺铂化疗的治疗指数,必须在优化肿瘤致敏的同时规避耐药性和毒性。癌细胞对顺铂产生耐药性的主要机制之一是通过上调 DNA 修复途径。在这篇综述中,我们讨论了顺铂诱导的 DNA 损伤背景下的 DNA 损伤反应。我们描述了参与该途径的蛋白质及其在耐药性发展中的作用。讨论了顺铂耐药的常见生物标志物及其用于改善患者风险分层和治疗个性化的方法。最后,我们讨论了一些当前的治疗方法和未来的策略,以避免顺铂耐药性的发展。
Platinum-based chemotherapies, such as cisplatin, play a large role in cancer treatment. The development of resistance and treatment toxicity creates substantial barriers to disease control, yet. To enhance the therapeutic index of cisplatin-based chemotherapy, it is imperative to circumvent resistance and toxicity while optimizing tumor sensitization. One of the primary mechanisms by which cancer cells develop resistance to cisplatin is through upregulation of DNA repair pathways. In this review, we discuss the DNA damage response in the context of cisplatin-induced DNA damage. We describe the proteins involved in the pathways and their roles in resistance development. Common biomarkers for cisplatin resistance and their utilization to improve patient risk stratification and treatment personalization are addressed. Finally, we discuss some of the current treatments and future strategies to circumvent the development of cisplatin resistance.
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