Combating Drug Resistance in Lung Cancer: Exploring the Synergistic Potential of Metformin and Cisplatin in a Novel Combination Therapy; A Systematic Review.

IF 3.3 4区 医学 Q3 CHEMISTRY, MEDICINAL Current topics in medicinal chemistry Pub Date : 2025-01-01 DOI:10.2174/0115680266317788241121100259
Emad Jafarzadeh, Behnam Omidi Sarajar, Armineh Rezaghol Lalani, Nima Rastegar-Pouyani, Shima Aliebrahimi, Vahideh Montazeri, Mohammad H Ghahremani, Seyed Nasser Ostad
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Abstract

Introduction: The persistent drug resistance observed in lung cancer necessitates innovative strategies to improve therapeutic outcomes. This review investigates the potential of combining metformin (Met) and cisplatin (Cis) to overcome drug resistance and enhance treatment efficacy. Cis's limitations, including drug resistance and adverse effects, coupled with Met's established safety profile, form the backdrop for this exploration.

Methods: Systematic literature searches across major databases identified relevant studies exploring the synergistic effects of Met and Cis in the context of drug-resistant lung cancer. Data extraction encompassed diverse facets, including treatment protocols, cellular responses, and mechanistic insights. The synthesis of these findings sheds light on the potential of this combination therapy to combat drug resistance.

Results: Numerous in vitro and in vivo studies have demonstrated the ability of the Met + Cis combination to sensitize drug-resistant lung cancer cells. The co-treatment consistently showed enhanced inhibition of cell proliferation, elevated apoptosis rates, and attenuated migration and invasion capabilities compared to monotherapies. Mechanistically, Met's modulatory effect on key pathways, such as AMPK-mTOR and ROS-mediated signaling, appears to underlie its ability to counter drug resistance.

Conclusion: The Met + Cis combination holds promise as an innovative strategy to counter drug resistance in lung cancer. By harnessing the synergistic effects of these agents, combination therapy offers a novel approach to enhance treatment efficacy and mitigate the challenges posed by drug-resistant lung cancer. Although further clinical validation is required, the Met + Cis synergy represents a promising avenue in the pursuit of improved lung cancer therapy outcomes.

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对抗肺癌耐药:探索二甲双胍与顺铂联合治疗的协同潜力系统评价。
导读:在肺癌中观察到的持续耐药需要创新的策略来改善治疗效果。本文综述了二甲双胍(Met)联合顺铂(Cis)克服耐药和提高治疗效果的潜力。Cis的局限性,包括耐药性和副作用,加上Met已建立的安全性,构成了这项探索的背景。方法:对主要数据库进行系统文献检索,确定Met和Cis在耐药肺癌中的协同作用的相关研究。数据提取包含多个方面,包括治疗方案、细胞反应和机制见解。这些发现的综合揭示了这种联合疗法对抗耐药性的潜力。结果:大量的体外和体内研究已经证明Met + Cis联合对耐药肺癌细胞的致敏能力。与单一治疗相比,联合治疗始终显示出增强的细胞增殖抑制,升高的细胞凋亡率,以及减弱的迁移和侵袭能力。从机制上讲,Met对关键通路的调节作用,如AMPK-mTOR和ros介导的信号传导,似乎是其抵抗耐药性能力的基础。结论:Met + Cis联合治疗有望成为对抗肺癌耐药的创新策略。通过利用这些药物的协同作用,联合治疗为提高治疗效果和减轻耐药肺癌带来的挑战提供了一种新的方法。虽然需要进一步的临床验证,但Met + Cis协同作用代表了追求改善肺癌治疗结果的有希望的途径。
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来源期刊
CiteScore
6.40
自引率
2.90%
发文量
186
审稿时长
3-8 weeks
期刊介绍: Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.
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