Abstract
Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, is the 4th most frequent cause of cancer-related death worldwide, primarily due to the inherent chemoresistant nature and metastatic capacity of this tumor. The latter is believed to be mainly due to the existence of a subpopulation of highly plastic “stem”-like cells within the tumor, known as cancer stem cells (CSCs), which have been shown to have unique metabolic, autophagic, invasive, and chemoresistance properties that allow them to continuously self-renew and escape chemo-therapeutic elimination. As such, current treatments for the majority of PDAC patients are not effective and do not significantly impact overall patient survival (<7 months) as they do not affect the pancreatic CSC (PaCSC) population. In this context, it is important to highlight the need to better understand the characteristics of the PaCSC population in order to develop new therapies to target these cells. In this review, we will provide the latest updates and knowledge on the inherent characteristics of PaCSCs, particularly their unique biological properties including chemoresistance, epithelial to mesenchymal transition, plasticity, metabolism and autophagy.
Highlights
The main difference between the two models is that the cancer stem cells (CSCs) “hierarchical” model proposes that a particular subset of tumor cells, with “stem-like” properties, are the sole drivers of tumor formation [26], metastatic dissemination, chemoresistance, and disease recurrence/relapse [27]
Current research in the field of cell biology, genetics, metabolism and immunology have created new hope for developing new tools for early diagnosis and for improving treatment of this disease; more research to better understand the biology of Pancreatic ductal adenocarcinoma (PDAC) is still needed
Our ever-expanding understanding of the pancreatic CSC (PaCSC) population and the role these cells play in all aspects of PDAC is promising
Summary
Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, is currently the fourth leading cause of cancer-related death in developed countries. By 2030, it is expected to become the second leading cause of cancer-related death, after non-small cell lung carcinoma, its incidence will not increase significantly to surpass the five most common cancers, lung, breast, prostate, colorectal and bladder cancer [1] These alarming statistics are due to the fact that there are no specific symptoms that can act as predictive indicators of this disease at an early stage. While successful early detection is necessary and has been shown to be a significant contributor in altering both the incidence and death rates in other solid tumors, the fact remains that the vast majority of PDAC patients are diagnosed with advanced-stage non-resectable disease. All of these cellular and non-cellular components fulfill different roles during PDAC tumorigenesis, evolution and progression such as development support, chemoresistance and CSC activation [22,23]
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