Ferroptosis in Cancer Research: From Lipid Peroxidation to Precision Therapeutics

Abstract

Ferroptosis has emerged as a novel iron-dependent form of regulated cell death with potential in oncological therapeutics. The excessive accumulation of iron in cancer cells leads to lipid peroxidation, induced cell death. In contrast to other forms of cell death viz. apoptosis, necroptosis and autophagy, ferroptosis occurs through distinct independent biochemical pathways providing novel targets for interventional therapy.However, research gaps in understanding of mechanisms and pathways leading to ferroptosis, role of tumor microenvironment, biomarkers and the challenges involved in combining it with other cancer therapy hinder its clinical translation. A bibliometric analysis highlighted research trends to understand gaps in Ferroptosis mechanisms, cancer therapy, tumor microenvironment, biomarkers, and innovative combination therapy challenges in the last twenty years. The inclusion and exclusion criteria were set. A surge in ferroptosis research was observed in the last five years with India still trying to pace up. Patient stratification for targeted precision therapies, resistance to ferroptosis and off-target effects are a challenge for translational applications in clinics. Lipid peroxidation, iron metabolism and novel compounds controlling ferroptosis have been explored. The review explores expected research on methods for selectively activating cancer cells to undergo ferroptosis, in response to their unique metabolic and oxidative stress profile. The work also aims to identify ferroptosis as a treatment option for conventionally treated non-responsive cancers. A traverse through the available literature and ongoing research highlights the prospects of ferroptosis as a robust and targeted antineoplastic strategy, paving the way for future therapeutic innovations.