Harald Mangge 1 , Tobias Niedrist 2 , Wilfried Renner 2 , Stefan Lyer 3 , Christoph Alexiou 3 , Johannes Haybaeck 4 . Show Affiliations »
Abstract
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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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 . Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Entities: Chemical
Disease
Species
Keywords:
Pancreatic ductal adenocarcinoma; genetic aspects; immunological aspects; metabolic aspects; nanomedical aspects; neural remodellingzzm321990aspects; new insights in stroma pdac cell interactions
Mesh: See more »
Year: 2017
PMID: 28494747 DOI: 10.2174/0929867324666170510150124
Source DB: PubMed Journal: Curr Med Chem ISSN: 0929-8673 Impact factor: 4.530