Background: Pancreatic ductal adenocarcinoma (PDAC) is devastating. Because
of its silent nature, the disease is often only diagnosed once it has reached an advanced, frequently
inoperable stage. To date, we have no biomarkers that facilitate earlier diagnosis,
leaving sufficient time for curative therapy that effectively lowers the very high mortality rate
of this cancer entity. Because of this, the life expectancy of patients with PDAC is low (i.e. ≤
6% five-year survival rates). New data, including particular genetic signatures and features of
the stromal architecture of PDAC tumors, may better explain their aggressiveness, their relatively
long-lasting painless expansion, and why chemotherapy so frequently fails. The typical
tumor-induced stromal desmoplasia is characterized by cancer-associated fibroblasts (CAFs),
decreased immune surveillance, cancer-associated neural remodeling, and a very low vascular
density. This stromal microenvironment generates hypoxia, nutrient deficiency, immune suppression,
and chemoresistance. The combination of factors results in a vicious disease that
begins with the long-lasting, asymptomatic development of a large tumor mass, followed by a
delayed diagnosis with a high percentage of inoperable states, exhibiting a poor response to
all conservative therapeutic options, including radiation, and which ends with metastasis resulting
in a rapid fatal outcome.
Objective: In this article, we review coherences on genetic, cellular, immunological, Nano
medical and stromal characteristics of PDAC tissue, and discuss metabolic abnormalities associated
with and/or preceding the tumor progression rate.
Conclusion: A more comprehensive understanding of the underlying mechanisms can improve
the diagnostic and therapeutic management of patients suffering from this devastating
type of cancer.