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药物基因组学对多药耐药蛋白1相关的癌症耐药性及创新药物递送方法的影响:推进精准肿瘤学发展

Pharmacogenomics influence on MDR1-associated cancer resistance and innovative drug delivery approaches: advancing precision oncology.

作者信息

Radhakrishnan Arun, Shanmukhan Nikhitha K, Samuel Linda Christabel

机构信息

Department of Pharmaceutics, JKKN College of Pharmacy, Kumarapalayam, Tamil Nadu, 638183, India.

Department of Conservative Dentistry and Endodontics, JKKN Dental College and Hospitals, Kumarapalayam, 638183, India.

出版信息

Med Oncol. 2025 Feb 6;42(3):67. doi: 10.1007/s12032-025-02611-w.

Abstract

Currently, there is a growing concern surrounding the treatment of cancer, a formidable disease. Pharmacogenomics and personalized medicine have emerged as significant areas of interest in cancer management. The efficacy of many cancer drugs is hindered by resistance mechanisms, particularly P-glycoprotein (P-gp) efflux, leading to reduced therapeutic outcomes. Efforts have intensified to inhibit P-gp efflux, thereby enhancing the effectiveness of resistant drugs. P-gp, a member of the ATP-binding cassette (ABC) superfamily, specifically the multidrug resistance (MDR)/transporter associated with antigen processing (TAP) sub-family B, member 1, utilizes energy derived from ATP hydrolysis to drive efflux. This review focuses on genetic polymorphisms associated with P-gp efflux and explores various novel pharmaceutical strategies to address this challenge. These strategies encompass SEDDS/SNEDDS, liposomes, immunoliposomes, solid lipid nanoparticles, lipid core nanocapsules, microemulsions, dendrimers, hydrogels, polymer-drug conjugates, and polymeric nanoparticles. The article aims to elucidate the interplay between pharmacogenomics, P-gp-mediated drug resistance in cancer, and formulation strategies to improve cancer therapy by tailoring formulations to genetically susceptible patients.

摘要

目前,人们对癌症(一种可怕的疾病)的治疗愈发关注。药物基因组学和个性化医疗已成为癌症管理中备受关注的重要领域。许多抗癌药物的疗效因耐药机制而受到阻碍,尤其是P-糖蛋白(P-gp)外排,导致治疗效果降低。抑制P-gp外排的工作已加强,从而提高耐药药物的有效性。P-gp是ATP结合盒(ABC)超家族的成员,具体属于多药耐药(MDR)/与抗原加工相关的转运蛋白(TAP)亚家族B成员1,它利用ATP水解产生的能量来驱动外排。本综述聚焦于与P-gp外排相关的基因多态性,并探索各种新颖的制药策略来应对这一挑战。这些策略包括自乳化药物传递系统/纳米自乳化药物传递系统、脂质体、免疫脂质体、固体脂质纳米粒、脂质核纳米胶囊、微乳、树枝状大分子、水凝胶、聚合物-药物偶联物和聚合物纳米粒。本文旨在阐明药物基因组学、癌症中P-gp介导的耐药性以及通过为基因易感性患者量身定制制剂来改善癌症治疗的制剂策略之间的相互作用。

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