Nanomedicine and epigenetics: New alliances to increase the odds in pancreatic cancer survival

• Published in: Biomedicine & pharmacotherapy Vol. 165; p. 115179
• Main Authors: Urbanova, Maria, Cihova, Marina, Buocikova, Verona, Slopovsky, Jan, Dubovan, Peter, Pindak, Daniel, Tomas, Miroslav, García-Bermejo, Laura, Rodríguez-Garrote, Mercedes, Earl, Julie, Kohl, Yvonne, Kataki, Agapi, Dusinska, Maria, Sainz, Bruno, Smolkova, Bozena, Gabelova, Alena
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.09.2023; Elsevier
• Subjects: Carcinoma, Pancreatic Ductal - drug therapy; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - pathology; Epigenetics; Humans; Nanomedicine; Nanomedicine immunosuppression; Nanoparticle Drug Delivery System; Pancreatic ductal adenocarcinoma; Pancreatic Neoplasms; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Tumor microenvironment; Tumor Microenvironment - genetics; Epigenetics; Nanomedicine immunosuppression; Tumor microenvironment; Pancreatic ductal adenocarcinoma
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.115179

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers worldwide, primarily due to its robust desmoplastic stroma and immunosuppressive tumor microenvironment (TME), which facilitate tumor progression and metastasis. In addition, fibrous tissue leads to sparse vasculature, high interstitial fluid pressure, and hypoxia, thereby hindering effective systemic drug delivery and immune cell infiltration. Thus, remodeling the TME to enhance tumor perfusion, increase drug retention, and reverse immunosuppression has become a key therapeutic strategy. In recent years, targeting epigenetic pathways has emerged as a promising approach to overcome tumor immunosuppression and cancer progression. Moreover, the progress in nanotechnology has provided new opportunities for enhancing the efficacy of conventional and epigenetic drugs. Nano-based drug delivery systems (NDDSs) offer several advantages, including improved drug pharmacokinetics, enhanced tumor penetration, and reduced systemic toxicity. Smart NDDSs enable precise targeting of stromal components and augment the effectiveness of immunotherapy through multiple drug delivery options. This review offers an overview of the latest nano-based approaches developed to achieve superior therapeutic efficacy and overcome drug resistance. We specifically focus on the TME and epigenetic-targeted therapies in the context of PDAC, discussing the advantages and limitations of current strategies while highlighting promising new developments. By emphasizing the immense potential of NDDSs in improving therapeutic outcomes in PDAC, our review paves the way for future research in this rapidly evolving field. [Display omitted] •Specific PDAC tumor microenvironment features contribute to its poor prognosis.•Targeting epigenetic pathways holds the potential for overcoming immunosuppression.•Nano-based drug delivery systems provide enhanced therapeutic capabilities.•These strategies show promise for stroma remodeling and better therapeutic response.•Future research in this evolving field paves the way for improved patient outcomes.