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克服卵巢癌顺铂耐药的治疗策略。

Therapeutic strategies to overcome cisplatin resistance in ovarian cancer.

机构信息

Department of Biopharmaceutical Sciences, Shanghai Ocean University, Shanghai, 201306, China.

出版信息

Eur J Med Chem. 2022 Mar 15;232:114205. doi: 10.1016/j.ejmech.2022.114205. Epub 2022 Feb 17.

Abstract

Ovarian cancer (OC) is one of the most common gynecologic tumors worldwide and one with the highest mortality. Cisplatin (DDP) is the first platinum-based complex approved by the Food and Drug Administration (FDA) to treat patients with OC. Despite a good initial response rate, most patients receiving DDP treatment will ultimately develop resistance via various complicated mechanisms, leading to therapeutic failure and increased mortality. Multiple resistance pathways have been identified as potentially key areas of intervention. In this review, chemotherapeutic drugs and phytochemicals developed to overcome cisplatin-resistance ovarian cancer (CROC) were discussed. Targeted inhibition or specific drugs are effective against the DDP-resistance phenotype by inhibiting resistance or increasing cytotoxic efficacy. Phytochemicals as chemosensitizers offer novel treatment strategies for CROC patients by reducing chemoresistance and increasing drug efficacy. Due to the complexity of the DDP-resistance mechanism, the treatment of OC needs to improve specificity and effectiveness, and multi-path cooperative therapy is undoubtedly one of the best options. We discuss extensively the role of combination therapy in reversing DDP-resistance in OC and the significance of using a nanoparticle delivery system in this context. Suggestions for potential therapeutic strategies for CROC treatment will help discover more effective and specific regimens to overcome DDP-resistance.

摘要

卵巢癌(OC)是全球最常见的妇科肿瘤之一,也是死亡率最高的肿瘤之一。顺铂(DDP)是美国食品和药物管理局(FDA)批准的第一种铂类复合物,用于治疗 OC 患者。尽管初始缓解率较高,但大多数接受 DDP 治疗的患者最终会通过各种复杂机制产生耐药性,导致治疗失败和死亡率增加。已经确定了多种耐药途径作为潜在的干预关键领域。在这篇综述中,讨论了开发用于克服顺铂耐药性卵巢癌(CROC)的化疗药物和植物化学物质。通过抑制耐药性或提高细胞毒性效力,靶向抑制或特定药物对 DDP 耐药表型有效。植物化学物质作为化疗增敏剂通过降低化疗耐药性和提高药物疗效,为 CROC 患者提供了新的治疗策略。由于 DDP 耐药机制的复杂性,OC 的治疗需要提高特异性和有效性,多途径协同治疗无疑是最佳选择之一。我们广泛讨论了联合治疗在逆转 OC 中 DDP 耐药性的作用,以及在这种情况下使用纳米颗粒递送系统的意义。对 CROC 治疗潜在治疗策略的建议将有助于发现更有效和更特异的方案来克服 DDP 耐药性。

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