Targeted therapy for pancreatic cancer: lessons learned and future opportunities

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is associated with a very poor prognosis because of its aggressive character, late-stage diagnosis, and resistance against systemic treatments. The current standard of care treatment for advanced PDAC is a combination of nab-paclitaxel and gemcitabine. However, other therapeutic approaches are necessary to combat cases where PDAC develops significant resistance against conventional chemotherapy. So far, targeted therapies have not been highlighted significantly with regards to facilitating successful treatment in PDAC patients. This review focuses on different targeted therapies tested in PDAC preclinically and clinically, such as antiangiogenic therapy, DNA repair inhibitors, KRAS pathway inhibitors, and anti-stromal therapy, summarizing data obtained regarding their implementation in treating PDAC, both by themselves and in combination with other drugs. This review also highlights recent advances in PDAC targeted therapies that may provide avenues for improved survival and facilitate further investigation into other potential therapeutic approaches in the future, including direct KRAS inhibitors, novel anti-stromal therapies, multikinase inhibitors, nanoparticle targeted therapy, and immunotherapy. Given the multifactorial nature of PDAC and how this disease has immense complexity in its treatment response with the development of resistance mechanisms, greater consideration and evaluation of novel targeted therapies are necessary towards improving PDAC treatment efficacy and patient outcomes.