Topic: Deciphering Therapeutic Resistance in Urological Cancers: Bridging Clonal Evolution, Microenvironment, and Multi-Omics for Clinical Translation

Therapeutic resistance remains a major challenge in urological cancers, limiting the efficacy of standard treatments and adversely affecting patient outcomes. Resistance emerges from complex, interconnected mechanisms, including clonal evolution under therapeutic pressure, immunosuppressive remodeling of the tumor microenvironment (TME), and treatment-induced cellular senescence. Senescent cells secrete senescence-associated secretory phenotype (SASP) factors that promote stemness, epithelial–mesenchymal transition (EMT), and drug tolerance. Additionally, dysregulated DNA damage response (DDR) pathways and epigenetic modifications further contribute to chemoresistance and radiotherapy resistance.

Recent advances in single-cell and multi-omics technologies, coupled with AI-driven integrative analyses, now enable unprecedented resolution to map tumor heterogeneity, TME dynamics, and molecular networks underlying therapeutic resistance. This Special Issue welcomes high-quality original research and comprehensive reviews that:

1. Elucidate the molecular and cellular mechanisms of resistance in urological cancers;

2. Identify predictive biomarkers of treatment response or resistance;

3. Develop innovative, pathway-targeted therapeutic strategies.

By highlighting these advances, the issue aims to accelerate the translation of mechanistic insights into effective, precision-guided interventions for patients with urological cancers.

Topics of interest include, but are not limited to:

1. TME, Immunosuppression, Epigenetic Regulation in Drug Resistance;

2. SASP and Its Role in Resistance;

3. Single-Cell and Multi-Omics Approaches for Dissecting Resistance Mechanisms;

4. AI-Driven Biomarker Discovery and Development of Targeted Therapeutics;

5. Clinical Trials or Case Studies Demonstrating Successful Translational Research to Overcome Resistance.