Pancreatic cancer stem cells and EMT in drug resistance and metastasis.
Pancreatic cancer (PC) is an aggressive malignancy with one of the worst outcomes among all cancers. It is the fourth leading cause of cancer death in the United States with a very low five-year survival rate. The high mortality of PC could, in part, be due to their drug resistance characteristics and high propensity for metastasis. Recently, cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT)-type cells, which shares molecular characteristics with CSCs, have been believed to play critical roles in drug resistance and cancer metastasis as demonstrated in several human malignancies including PC. Thus, the discovery of molecular knowledge of drug resistance and metastasis in relation to CSCs and EMT in PC is becoming an important area of research, and such knowledge is likely to be helpful in the discovery of newer drugs as well as designing novel therapeutic strategies for the treatment of PC with better outcome. In this brief review, we will summarize the current knowledge regarding the CSCs and EMT in the context of drug resistance and metastasis in PC, the molecular events occurring in CSCs and EMT, and the design of novel therapeutic strategies targeting CSCs and EMT-type cells to increase drug sensitivity and suppression of metastasis toward better treatment outcome of patients diagnosed with PC.
Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA. fsarkar@med.wayne.edu
F H
FH
Sarkar
Y
Y
Li
Z
Z
Wang
D
D
Kong
D000818:Animals; D019008:Drug Resistance, Neoplasm; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D008648:Mesoderm / Q000166:cytology* / Q000187:drug effects* / Q000473:pathology; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*