Preclinical studies identified actionable routes to reverse resistance to platinum chemotherapy: targeting FBXL5 sensitized iron-rich colorectal tumors to oxaliplatin via ferroptosis mechanisms, while modulation of STK19 increased cisplatin efficacy in tongue squamous cell carcinoma. Both reports used mechanistic genomics and functional assays to nominate translational targets. The FBXL5 work demonstrated that manipulating iron-regulatory pathways can re-engage cell-death programs in otherwise refractory tumors, suggesting combination strategies with ferroptosis inducers. STK19 studies used CRISPR-based approaches to show genetic modulation can alter DNA damage response and chemotherapy sensitivity. If these targets validate in vivo and in early clinical studies, pharma and biotech could pursue small-molecule or biologic modulators as chemosensitizers, opening near-term combination trial opportunities in common solid tumors.