Investigating the Efficacy of a Combination Therapy and a Nanopolymer-Mediated Drug Delivery Approach to Treat Pancreatic and Breast Cancer
Pancreatic ductal adenocarcinoma (PDAC) is one of the most challenging malignancies to treat clinically. The current standard of care for a possible cure requires surgery; however, only a small subset of patients is eligible for potentially curable surgery, and chemotherapy or radiation therapy are typically used in a palliative fashion. Although modest improvements are observed for a short period of time, treatment failure inevitably results. This lack of success has been attributed to the highly mutagenic and adaptive nature of pancreatic cancer. As a possible solution to this, we hypothesize that supplementing conventional chemotherapeutics with agents that broadly target multiple pathways implicated in multistage tumorigenesis may lead to improvements in treatment outcomes. We propose to investigate the efficacy of a triple combination of metformin (Met), acetylsalicylic acid (ASA), and oseltamivir phosphate (OP) together with gemcitabine and paclitaxel to treat pancreatic cancer. Owing to the broad applicability of this combination, we also investigated its translatability to triple negative breast cancer (TNBC). TNBC is characterized by its poor prognosis, early relapse, and a shorter progression-free survival period following recurrence. The development of chemoresistance is another common clinical challenge with breast cancer in that conventional treatments could select for resistant subpopulation leading to a more aggressive malignancy challenging to treat. Engineering of a “smart” drug delivery system to specifically target tumour cells has been at the forefront of cancer research. Here, we investigated the efficacy of a functionalized folic acid-conjugated amphiphilic alternating copolymer (FA-DABA-SMA) to target three-dimensional avascular human pancreatic and breast tumour spheroids in culture and deliver hydrophobic agents. The findings of this research provide supporting evidence for the efficacy and translatability of this combination treatment approach in offering improved survival outcomes in patients with pancreatic and breast cancer.
URI for this recordhttp://hdl.handle.net/1974/27581
Request an alternative formatIf you require this document in an alternate, accessible format, please contact the Queen's Adaptive Technology Centre
The following license files are associated with this item: