Current and Future Therapies for Pancreatic Ductal Adenocarcinoma

SIMPLE SUMMARY: Pancreatic cancer is the fourth leading cause of cancer-related mortality worldwide. The poor survival associated with this disease is due to delayed diagnosis, a lack of reliable biomarkers, and tumour resistance to treatment. Currently, surgery is the only curative treatment option, but few patients are eligible for this procedure. Developing resistance to current chemotherapies such as gemcitabine has led to a reduction in effective therapy options for patients and an urgent requirement for the development of novel therapeutic avenues. Potential success has been noted in therapeutic approaches such as synthetic lethality and immunotherapy. An array of clinical trials are currently recruiting, primarily in the area of monoclonal antibodies in combination with other therapies such as chemotherapy and immune checkpoint inhibitors. This review article aims to highlight the potential these therapies have to improve patient prognosis and survival. ABSTRACT: Pancreatic cancer is one of the leading causes of cancer-related death worldwide. This is due to delayed diagnosis and resistance to traditional chemotherapy. Delayed diagnosis is often due to the broad range of non-specific symptoms that are associated with the disease. Resistance to current chemotherapies, such as gemcitabine, develops due to genetic mutations that are either intrinsic or acquired. This has resulted in poor patient prognosis and, therefore, justifies the requirement for new targeted therapies. A synthetic lethality approach, that targets specific loss-of-function mutations in cancer cells, has shown great potential in pancreatic ductal adenocarcinoma (PDAC). Immunotherapies have also yielded promising results in the development of new treatment options, with several currently undergoing clinical trials. The utilisation of monoclonal antibodies, immune checkpoint inhibitors, adoptive cell transfer, and vaccines have shown success in several neoplasms such as breast cancer and B-cell malignancies and, therefore, could hold the same potential in PDAC treatment. These therapeutic strategies could have the potential to be at the forefront of pancreatic cancer therapy in the future. This review focuses on currently approved therapies for PDAC, the challenges associated with them, and future directions of therapy including synthetically lethal approaches, immunotherapy, and current clinical trials.