Targeting Glutathione Peroxidase 4 in Drug-Tolerant Persister Cells: Emerging Insights in Cancer Therapy

Abstract

Author(s): Naina Bhoyar, Poorti Sharma, Prachi Gurudiwan

Cancer continues to pose a substantial worldwide health burden, hence requiring the advancement of novel treatment strategies. Resistance to conventional cancer treatments is a common occurrence, partially ascribed to the existence of Drug-Tolerant persistent cells (DTPCs). These cellular entities, constituting a minor proportion of the populace, possess the ability to withstand therapeutic interventions and instigate a recurrence of cancer. The current work aims to explore the recent advancements in cancer treatment by explicitly targeting Glutathione Peroxidase 4 (GPX4) in DTPCs. The current methodologies have encountered difficulties in effectively addressing DTPCs, resulting in obstacles in attaining sustained remission over an extended period. The GP-DTPC technique, which is being offered, presents a unique approach aimed at improving the survival rate, expression of drug efflux pumps, clonogenic survival, and reduction of Reactive Oxygen Species (ROS) levels in drug-tolerant persister cells. The GP-DTPC exhibits a mean performance with a Survival Rate of 88.55%, Drug Efflux Pump Expression of 1.64, Clonogenic Survival of 88.55%, ROS Levels of 234.27, and Mitophagy Activity of 1.49, surpassing other methodologies. The findings indicate the potential efficacy of targeting GPX4 in DTPCs, which might provide a novel strategy for addressing cancer, reducing the risk of recurrence, and enhancing long-term patient prognosis. This work explores novel approaches in cancer therapy by investigating the mechanisms behind the long-term survival and resistance to drugs shown by persister cells

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