SLC7A11 as a molecular nexus of prognosis, resistance, and therapeutic roadmap in cancer: A systematic review and meta-analysis.

Solute Carrier Family 7 Member 11 (SLC7A11), a redox homeostasis and metabolism regulator, is frequently overexpressed and mutated in cancers, contributing to progression and therapy resistance. This study systematically reviewed and meta-analyzed its prognostic value, mutational landscape, role in resistance, and its therapeutic potential. A comprehensive search (2010-2024) across PubMed and ScienceDirect identified 236 studies, alongside TCGA data from 30 cancer types and 128 mutations from GDC. Prognostic and clinicopathological correlations were assessed using hazard ratios (HRs), with fixed/random effects models based on heterogeneity (I), and significance tested via Z-tests (p < 0.05). Publication bias was evaluated using Begg's and Egger's tests. General linear models explored associations with resistance and pathway alterations. Interestingly, SLC7A11 overexpression was associated with poor prognosis (HR = 1.22), adverse clinicopathological features viz. TNM-stage and therapy resistance like chemoresistance (p < 0.001). Mutation analysis revealed diverse alterations and frequent heterozygous deletions, prevalently, missense mutation underscoring its oncogenic role. Moreover, SLC7A11 inhibitors, particularly sulfasalazine and erastin, effectively reversed resistance, in 18 clinical trials (Phase I-III) completed over the last decade. Targeting SLC7A11 presents a promising therapeutic strategy to modulate redox balance, metabolism, and ferroptosis, towards efficient cancer treatments.