Scientific rationale for integrative and personalised strategies for pancreatic ductal adenocarcinoma management

Abstract

Pancreatic ductal adenocarcinoma (PDAC) arises from epithelia of pancreas. Despite its low incidence, it is the most lethal cancer type. Although the poor outcome is largely secondary to the high proportion of patients who are diagnosed with advanced disease, the prognosis of PDAC is also influenced by the inherent biological aggressiveness and the high metastatic potential of this malignancy. Treatment options remain limited with little progress over the last decades. Some improvements in surgical outcome occur in patients who also receive chemotherapy and/or radiotherapy, however, the impact on long-term survival has been minimal owing to the intense resistance of PDAC to all extent treatments regimen. Hence, there is an urgent need to 1) gain better understanding of the biology of PDAC; 2) to develop early detection and prevention programs; 3) to identify new therapeutic strategies to improve quality of life and survivorship. In this review, first, we will summarise the state of knowledge of PDAC pathogenesis with a particular the focus on the molecular characteristics causing therapeutic resistance. Then, we will briefly review current and emerging approaches in the PDAC care. Lastly, we will highlight the integrative approaches in the light of new experimental and clinical research conducted with the aim of moving towards personalised therapy in patients with PDAC.

Pleiotropic Effects of Heparins: From Clinical Applications to Molecular Mechanisms in Hepatocellular Carcinoma

“…PM implements “-omic" sciences (genomics, epigenomics, transcriptomics, proteomics, etc.) to integrate various data sets with the aim of dissecting molecular signatures and functional pathways that help to classify tumor subtypes and determine their natural course, prognosis, and responsiveness to therapies [ 64 ]. Thus, stratification of the subset of patients who might respond to particular combinations of therapies is crucial in the management of cancer.…”

Metastasis Suppressor Genes in Pancreatic Cancer

“…Pancreatic ductal adenocarcinoma tumor cells have also been reported to use PSC as part of a support network to aid in dissemination to the target organs. 29 Pancreatic stellate cells manipulate the target site microenvironment to create conducive conditions for PDAC tumor cell growth and proliferation. In addition, PDAC tumor cells recruit and manipulate stromal fibroblasts, activating them to cancer-associated fibroblast, which release cytokines, ECM proteins, and other essential factors to promote PDAC metastasis at the target organs.…”

“…Pancreatic ductal adenocarcinoma tumor cells cocultured with PSC showed reduced expression of cell adhesion proteins, exhibited EMT, and increased motility. Pancreatic ductal adenocarcinoma tumor cells have also been reported to use PSC as part of a support network to aid in dissemination to the target organs 29 . Pancreatic stellate cells manipulate the target site microenvironment to create conducive conditions for PDAC tumor cell growth and proliferation.…”