Molecular predictors for the course of disease and individualized therapy in pancreatic cancer

Abstract

The understanding of the development of pancreatic cancer has undergone considerable development over the last two decades. This is mainly due to the progress and use of methods for molecular biological analysis of pancreatic carcinomas. There is now afundamental understanding with respect to the genetic drivers for the development of pancreatic cancer and the correlation with clinical data as well as the classification of different genetic characteristics of individual tumors even enables an estimation of the prognosis in some cases. The most common mutation in ductal adenocarcinoma, which if found in >90% of tumors, is the mutation of the KRAS oncogene. The other three, CDKN2A, p53 and SMAD4, are all tumor suppressor genes and are mutated in approximately 90%, 70% and 50% of carcinomas, respectively. In addition, genetic mutations predisposing to pancreatic cancer have been identified. Among the most important are BRCA2, p16/CDKN2A, STK11, PRSS1, PALP2, FANCC, FANCG and ATM. The classification of different subtypes and the knowledge of individual mutations (especially BRCA) can also be used to assess the response to treatment in individual cases. This applies to "conventional" combination chemotherapies (especially FOLFIRINOX) and also to targeted treatment approaches with tyrosine kinase inhibitors, PARP inhibitors and PD‑1 inhibitors. If knowledge about the course of the disease and decisions on individual therapies become established in everyday clinical practice in the future, this may also have adecisive impact on surgery as the most important pillar of curative treatment. This ranges from the increased achievement of secondary operability to the expansion of indications with respect to resection even in patients with metastases.