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

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.