The molecular biology of pancreatic adenocarcinoma: translational challenges and clinical perspectives

Abstract

Pancreatic cancer is an increasingly common cause of cancer mortality with a tight correspondence between disease mortality and incidence. Furthermore, it is usually diagnosed at an advanced stage with a very dismal prognosis. Due to the high heterogeneity, metabolic reprogramming, and dense stromal environment associated with pancreatic cancer, patients benefit little from current conventional therapy. Recent insight into the biology and genetics of pancreatic cancer has supported its molecular classification, thus expanding clinical therapeutic options. In this review, we summarize how the biological features of pancreatic cancer and its metabolic reprogramming as well as the tumor microenvironment regulate its development and progression. We further discuss potential biomarkers for pancreatic cancer diagnosis, prediction, and surveillance based on novel liquid biopsies. We also outline recent advances in defining pancreatic cancer subtypes and subtype-specific therapeutic responses and current preclinical therapeutic models. Finally, we discuss prospects and challenges in the clinical development of pancreatic cancer therapeutics.

Consistent Response on Challenge and Rechallenge of Liposomal Irinotecan in a Patient with Metastatic Pancreatic Adenocarcinoma Previously Treated with Gemcitabine plus Nab-Paclitaxel: A Case Report

“…Pancreatic cancer is a well-known dense stromal tissue malignancy, which explains the difficulty in anticancer therapy penetration and many clinical trial failure. However, several molecular factors are under investigation [ 15 ]. The POLO trial, which involved the identification of germline BRCA mutations and used a targeted therapy, proved to be effective, and such approaches are worth further exploration.…”

Treatment optimization of locally advanced and metastatic pancreatic cancer (Review)

“…Although cancer gene amplification mainly occurs in the earlier disease phases, genomic instability is maintained throughout the different steps of the metastatic cascade, and the genetic heterogeneity found in the different sites of metastases may stem from the primary non-metastatic tissue, since the distinct clones are shown to be already present in this tissue. Thus, early genomic events in the tumor evolution can determine the later molecular subtypes of PDAC ( 36 ).…”

Mitophagy-Related Gene Signature for Prediction Prognosis, Immune Scenery, Mutation, and Chemotherapy Response in Pancreatic Cancer

“…Emerging evidence has reported that targeted therapy based on genetic testing may provide an effective treatment option to overcome these drawbacks during PC therapy (Dokus et al, 2020). Nevertheless, most gene expression variations remain poorly characterized due to their complex molecular subtyping and tumor heterogeneity in PC patients, restraining their clinical translation (Hosein et al, 2020;Giuliani et al, 2021;Wang et al, 2021). Accordingly, a novel biomarker is urgently required for prognostic stratification and therapeutic purposes to enhance the outcome of the PC patients.…”