TY - JOUR
T1 - Biological and clinical relevance of stem cells in pancreatic adenocarcinoma
AU - Rasheed, Zeshaan A.
AU - Matsui, William
PY - 2012/3
Y1 - 2012/3
N2 - Cancer stem cells (CSC) have been identified in a growing number of human malignancies. CSC are functionally defined by their ability to self-renew and recapitulate tumors in the ectopic setting, and a growing number of studies have shown that they display other functional characteristics, such as invasion and drug resistance. These unique functional properties implicate a role for CSC in clinical consequences, such as initial tumor formation, relapse following treatment, metastasis, and resistance, suggesting they are a major factor in directing clinical outcomes. Pancreatic adenocarcinoma is a highly-aggressive disease with a propensity for early metastasis and drug resistance. Tumorigenic pancreatic cancer cells have been identified using the cell surface antigens CD44, CD24, and CD133, as well as the high expression of aldehyde dehydrogenase (ALDH). In vitro and in vivo studies have shown that ALDH- and CD133-expressing pancreatic CSC have a greater propensity for metastasis, and ALDH-expressing CSC have been shown to be resistant to conventional chemotherapy. In clinical samples from patients with resected pancreatic adenocarcinoma, the presence of ALDH-expressing CSC was associated with worse overall survival. The development of CSC-targeting therapies might be important in changing the clinical outcomes of patients with this disease, and others and we have begun to identify novel compounds that block CSC function. This review will discuss the biological and clinical relevance of CSC in pancreatic cancer, and will discuss novel therapeutic strategies to target them.
AB - Cancer stem cells (CSC) have been identified in a growing number of human malignancies. CSC are functionally defined by their ability to self-renew and recapitulate tumors in the ectopic setting, and a growing number of studies have shown that they display other functional characteristics, such as invasion and drug resistance. These unique functional properties implicate a role for CSC in clinical consequences, such as initial tumor formation, relapse following treatment, metastasis, and resistance, suggesting they are a major factor in directing clinical outcomes. Pancreatic adenocarcinoma is a highly-aggressive disease with a propensity for early metastasis and drug resistance. Tumorigenic pancreatic cancer cells have been identified using the cell surface antigens CD44, CD24, and CD133, as well as the high expression of aldehyde dehydrogenase (ALDH). In vitro and in vivo studies have shown that ALDH- and CD133-expressing pancreatic CSC have a greater propensity for metastasis, and ALDH-expressing CSC have been shown to be resistant to conventional chemotherapy. In clinical samples from patients with resected pancreatic adenocarcinoma, the presence of ALDH-expressing CSC was associated with worse overall survival. The development of CSC-targeting therapies might be important in changing the clinical outcomes of patients with this disease, and others and we have begun to identify novel compounds that block CSC function. This review will discuss the biological and clinical relevance of CSC in pancreatic cancer, and will discuss novel therapeutic strategies to target them.
KW - Cancer stem cell
KW - Drug resistance
KW - Metastasis
KW - Pancreatic cancer
UR - http://www.scopus.com/inward/record.url?scp=84856967625&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856967625&partnerID=8YFLogxK
U2 - 10.1111/j.1440-1746.2011.07015.x
DO - 10.1111/j.1440-1746.2011.07015.x
M3 - Review article
C2 - 22320910
AN - SCOPUS:84856967625
VL - 27
SP - 15
EP - 18
JO - Journal of Gastroenterology and Hepatology (Australia)
JF - Journal of Gastroenterology and Hepatology (Australia)
SN - 0815-9319
IS - SUPPL.2
ER -