FERROPTOSIS INDUCERS COMBINED WITH STANDARD CHEMOTHERAPY IN RESISTANT SOLID TUMORS: A META-ANALYSIS OF THERAPEUTIC EFFICACY AND SURVIVAL MARKERS

Resistance to conventional chemotherapy is the leading cause of treatment failure in solid tumors due to the evasion of apoptosis. Ferroptosis—a regulated form of cell death dependent on iron and lipid peroxidation—represents a metabolic vulnerability that can be exploited to reverse this refractory phenotype. This systematic review and meta-analysis evaluated the therapeutic efficacy and impact on survival of ferroptosis inducers combined with standard chemotherapy versus chemotherapy alone in models of resistant solid tumors, following the PRISMA 2020 guidelines. A search was conducted in PubMed. Ten comparative studies in colorectal, breast, pancreatic, ovarian, lung, and glioblastoma cancer models met the eligibility criteria. The Standardized Mean Difference was calculated using Hedges’ g under DerSimonian-Laird random-effects models. Methodological quality was assessed using SYRCLE.
The meta-analysis demonstrated a significant tumor reduction in favor of the combination (Hedges' g = -1.343; 95% CI: -1.700 to -0.985; p < 0.0001), with no statistical heterogeneity (Q = 1.05, df = 9, p = 0.998; I² = 0.0%). Sensitization was associated with the suppression of the SLC7A11 transporter and glutathione peroxidase 4 (GPX4), an increase in tissue malondialdehyde, and a decrease in Ki-67. Longitudinal models demonstrated prolonged progression-free survival. In conclusion, the co-administration of ferroptosis inducers overcomes chemoresistance in solid tumors, providing quantitative evidence for future rescue clinical trials.