KRT17: A Key Driver of Cancer Therapy Resistance and Emerging Therapeutic Target.

Keratin 17 (KRT17), a type I intermediate filament protein normally restricted to basal epithelia and hair follicles, is aberrantly overexpressed across diverse aggressive malignancies where it correlates strongly with poor prognosis. Beyond driving core oncogenic processes like cell proliferation, migration, apoptosis evasion, and metabolic reprogramming, KRT17 is increasingly recognized as a pivotal regulator of cancer therapy resistance. Mechanistically, KRT17 induces chemoresistance in multiple cancers through distinct pathways: activating AKT/ERK signaling and epithelial-mesenchymal transition (EMT) in bladder cancer; modulating Wnt/β-catenin in triple-negative breast cancer; influencing the EMT/Snail2/E-cadherin axis in cervical cancer; and engaging FAK/SRC/ERK/CXCL8 immunosuppression in pancreatic cancer. It also contributes to resistance in gastric, thyroid, and skin cancers via EMT, AKT/mTOR, and immune evasion. While KRT17 predominantly drives therapy resistance and immunosuppression across various malignancies, it exhibits a contrasting, context-dependent role in colorectal cancer, where its expression is associated with enhanced T-cell infiltration and improved response to immunotherapy. Given its cancer-specific overexpression, multifaceted role in malignancy (including resistance), and promising preclinical evidence that targeting KRT17 can reverse resistance, KRT17 emerges as a significant diagnostic/prognostic biomarker and a compelling therapeutic target. This review critically synthesizes evidence for KRT17's role in drug resistance and evaluates its potential for overcoming this major barrier to successful cancer treatment.