Current Clinical Strategies of Pancreatic Cancer Treatment and Open Molecular Questions

Abstract

Pancreatic cancer is one of the most lethal malignancies and is associated with a poor prognosis. Surgery is considered the only potential curative treatment for pancreatic cancer, followed by adjuvant chemotherapy, but surgery is reserved for the minority of patients with non-metastatic resectable tumors. In the future, neoadjuvant treatment strategies based on molecular testing of tumor biopsies may increase the amount of patients becoming eligible for surgery. In the context of non-metastatic disease, patients with resectable or borderline resectable pancreatic carcinoma might benefit from neoadjuvant chemo- or chemoradiotherapy followed by surgeryPatients with locally advanced or (oligo-/poly-)metastatic tumors presenting significant response to (neoadjuvant) chemotherapy should undergo surgery if R0 resection seems to be achievable. New immunotherapeutic strategies to induce potent immune response to the tumors and investigation in molecular mechanisms driving tumorigenesis of pancreatic cancer may provide novel therapeutic opportunities in patients with pancreatic carcinoma and help patient selection for optimal treatment.

Keywords: chemoradiation; chemotherapy; immunotherapy; molecular mechanism; pancreatic cancer; surgery; therapeutic targets; treatment options.

Figure 1

(a) Current treatment strategies for pancreatic carcinomas; (b) assumed future treatment strategy for pancreatic carcinoma: The most distinctive changes (highlighted in red) are probably (1) an extension of biopsy options and an introduction of routinely molecular tests including chemotherapy sensitivity, (2) an introduction of neoadjuvant therapy even in resectable stage, (3) an improvement of chemotherapy regimens with increased secondary resectability, and (4) the “introduction” of oligometastasis as the fifth subgroup (besides resectable, borderline, locally advanced, and metastatic stages) with enhanced therapy options including surgery in this new group. Dotted frames indicate possible therapy options.

Figure 2

Overview of important aspects in immunotherapy and molecular pathology of pancreatic ductal adenocarcinoma.