Conquering chemoresistance in pancreatic cancer: Exploring novel drug therapies and delivery approaches amidst desmoplasia and hypoxia

Pancreatic cancer poses a significant challenge within the field of oncology due to its aggressive behaviour, limited treatment choices, and unfavourable outlook. With a mere 10% survival rate at the 5-year mark, finding effective interventions becomes even more pressing. The intricate relationship between desmoplasia and hypoxia in the tumor microenvironment further complicates matters by promoting resistance to chemotherapy and impeding treatment efficacy. The dense extracellular matrix and cancer-associated fibroblasts characteristic of desmoplasia create a physical and biochemical barrier that impedes drug penetration and fosters an immunosuppressive milieu. Concurrently, hypoxia nurtures aggressive tumor behaviour and resistance to conventional therapies. a comprehensive exploration of emerging medications and innovative drug delivery approaches. Notably, advancements in nanoparticle-based delivery systems, local drug delivery implants, and oxygen-carrying strategies are highlighted for their potential to enhance drug accessibility and therapeutic outcomes. The integration of these strategies with traditional chemotherapies and targeted agents reveals the potential for synergistic effects that amplify treatment responses. These emerging interventions can mitigate desmoplasia and hypoxia-induced barriers, leading to improved drug delivery, treatment efficacy, and patient outcomes in pancreatic cancer. This review article delves into the dynamic landscape of emerging anticancer medications and innovative drug delivery strategies poised to overcome the challenges imposed by desmoplasia and hypoxia in the treatment of pancreatic cancer. •Pancreatic cancer is highly aggressive, with significant rates of relapse, metastasis, and resistance to chemotherapy, making it a leading cause of cancer-related deaths globally.•Desmoplasia and hypoxia play critical roles in chemotherapy resistance in pancreatic cancer, prompting research into their mechanisms and the development of innovative drug delivery methods to overcome these obstacles.•Nanomedicine shows promise in improving drug delivery to pancreatic tumours, reducing side effects, and enabling the creation of combination therapies with multiple drugs.•Combination therapy, supported by nanomedicine, utilizes the synergistic effects of different drugs to target various resistance mechanisms, increasing the chances of overcoming chemotherapy resistance in pancreatic cancer treatment.•Advanced drug delivery syste