Uncovering metabolic reprogramming in ovarian and cervical cancers with multi-omics.

Ovarian cancer (OC) and cervical cancer (CC) are major causes of gynecological malignancy mortality, but their spatially resolved metabolic features and shared progression-driving metabolic reprogramming remain unexplored. This study integrated spatial metabolomics, proteomics, and targeted metabolomics with in vitro assays to explore their metabolic reprogramming and therapeutic targets. The results revealed that OC exhibits intratumoral metabolic heterogeneity and suppresses tryptophan and vitamin B6 metabolism, with ferroptosis-related proteins upregulated in metastatic lesions and ALDH7A1/GATM knockdown promoting its cell proliferation and migration. CC progression was marked by amino acid and bile acid accumulation and neomenthol-driven cell proliferation. Purine metabolism activation was identified as a shared hallmark of both cancers, and purine nucleoside phosphorylase (PNP) knockdown was found to inhibit the proliferation of both OC and CC cells. This work identifies stage-specific metabolic vulnerabilities and PNP as a conserved therapeutic target, providing a framework for developing tailored gynecological cancer therapies.