Pharmacotherapeutic strategies for treating pancreatic cancer: advances and challenges

ABSTRACT

Introduction: Despite many efforts to improve the outcome of pancreatic ductal adenocarcinoma (PDAC), its prognosis remains poor, which is mostly related to late diagnosis and drug resistance. Improving systemic therapy is considered the major challenge in improving the outcome of this disease.

Areas covered: This review covers novel chemotherapy and targeted agents in the treatment of PDAC, with a focus on advanced stage disease.

Expert opinion: Current frontline therapies used in the treatment of patients with PDAC with favorable performance status are gemcitabine (GEM) and nab-paclitaxel or 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX). PDAC has a number of genetic mutations that may explain its biological behavior, such as KRAS, p53 and CDK2NA, which occur in more than 90% of cases. Unfortunately, to this day, a specific targeting agent to any of those frequent gene mutations is lacking. Emerging areas of targeted therapies include the DNA repair, stroma, metabolism, and stem cells. Immunotherapy with either vaccines or immune checkpoint inhibitors has not produced any significant improvements in outcome of PDAC. Incorporating different approaches in therapy, including conventional, immunological, and others, is key in offering patients with the best possible care.

KEYWORDS:

• Chemotherapy
• immunotherapy
• pancreatic cancer
• pathway
• stroma

Article highlights

• Pancreatic cancer is a lethal disease with no current established screening methods to detect it in early stages.

• Chemotherapy continues to be the mainstay of treatment and the need for novel therapy has not been fulfilled.

• Although several attempts were investigated to inhibit KRAS, it remains an elusive target. Focus is shifted to targeting downstream pathways.

• The utility of checkpoint inhibitors in the treatment of pancreatic cancer is currently restricted to the setting of mismatch repair tumors.

Declaration of interest

PA Philip acknowledges research support financing from Celgene, Bristol-Myers Squibb, Karyopharm Therapeutics, Ipsen, Novartis, Merck & Co., Eli Lilly and Company, Gilead Sciences, QED, Halozyme, Tyme Inc, and AstraZeneca. He has also received speaker fees from Celgene, Bristol-Myers Squibb, Ipsen, Amgen Inc and Novartis and has acted as a consultant for Rafael, Celgene, Merck & Co., Caris, Erytech, Lexicon, Halozyme, Aslan and Blueprint. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.