Ovarian cancer remains one of the most aggressive and fatal gynecologic malignancies, characterized by high rates of recurrence and poor long-term survival, largely attributable to the emergence of multidrug resistance. Although significant progress has been made in cytoreductive surgical techniques and platinum- and taxane-based chemotherapy, as well as the incorporation of targeted therapies and immunotherapies, therapeutic resistance remains a formidable obstacle in clinical management. The multifactorial nature of drug resistance encompassing genetic alterations, epigenetic reprogramming, metabolic adaptations, and the influence of the tumor microenvironment demands a deeper mechanistic understanding to inform the development of next-generation therapeutic strategies.
This special issue seeks to present a comprehensive and cutting-edge synthesis of recent advances in elucidating the molecular and cellular determinants of drug resistance in ovarian cancer. We welcome original research articles, authoritative reviews, and expert perspectives focusing on the identification and validation of predictive biomarkers, elucidation of chemoresistance and targeted therapy resistance pathways, design of novel nanotechnology-enabled drug delivery systems, and rational combinatorial treatment approaches aimed at circumventing resistance and improving clinical outcomes.
Relevant topics related to this special issue:
1. Mechanisms of Drug Resistance
• Molecular mechanisms underlying platinum and taxane resistance
• Role of epithelial-mesenchymal transition (EMT) and cancer stem cells in drug resistance
• DNA damage repair pathways (BRCA mutations, homologous recombination deficiency) and therapy resistance
• Epigenetic regulation contributing to chemoresistance
• Metabolic reprogramming and its role in drug resistance
• Exosomal communication in transferring drug-resistant phenotypes
2. Tumor Microenvironment and Drug Resistance
• Impact of hypoxia, immune evasion, and stromal interactions
• Role of cancer-associated fibroblasts and extracellular matrix
• Tumor immune microenvironment and immune checkpoint resistance
3. Novel Biomarkers for Predicting Drug Response
• Genomic, transcriptomic, proteomic, and metabolomic signatures
• Liquid biopsy-based biomarkers (ctDNA, circulating exosomes)
• Role of non-coding RNAs (miRNAs, lncRNAs, circRNAs) in drug resistance
4. Overcoming Drug Resistance: Therapeutic Innovations
• Novel small molecules targeting resistant pathways
• Repurposing old drugs to overcome chemoresistance
• Combination therapies with PARP inhibitors, PI3K inhibitors, and immune checkpoint inhibitors
• Nanotechnology-based drug delivery systems targeting drug-resistant ovarian cancer cells
5. Immunotherapy and Resistance
• Mechanisms of resistance to immune checkpoint inhibitors
• CAR-T and NK cell therapies for drug-resistant ovarian cancer
• Tumor immune escape mechanisms
6. Clinical Advances and Challenges
• Current clinical trials targeting drug-resistant ovarian cancer
• Translating bench side discoveries into bedside therapies
• Real-world challenges in managing drug-resistant ovarian cancer patients
7. Future Perspectives
• Personalized and precision medicine approaches
• Artificial intelligence and machine learning in predicting drug resistance
• Multi-omics integration for developing predictive models
