TY - JOUR
T1 - Thymidine Phosphorylase in Cancer; Enemy or Friend?
AU - Elamin, Yasir Y.
AU - Rafee, Shereen
AU - Osman, Nemer
AU - O′Byrne, Kenneth J.
AU - Gately, Kathy
N1 - Publisher Copyright:
© 2015, Springer Science+Business Media Dordrecht.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - Thymidine phosphorylase (TP) is a nucleoside metabolism enzyme that plays an important role in the pyrimidine pathway.TP catalyzes the conversion of thymidine to thymine and 2-deoxy-α-D-ribose-1-phosphate (dRib-1-P). Although this reaction is reversible, the main metabolic function of TP is catabolic. TP is identical to the angiogenic factor platelet-derived endothelial-cell growth factor (PD-ECGF). TP is overexpressed in several human cancers in response to cellular stressful conditions like hypoxia, acidosis, chemotherapy and radiotherapy. TP has been shown to promote tumor angiogenesis, invasion, metastasis, evasion of the immune-response and resistance to apoptosis. Some of the biological effects of TP are dependent on its enzymatic activity, while others are mediated through cytokines like interleukin 10 (IL-10), basic fibroblast growth factor (bFGF) and tumour necrosis factor α (TNFα). Interestingly, TP also plays a role in cancer treatment through its role in the conversion of the oral fluoropyrimidine capecitabine into its active form 5-FU. TP is a predictive marker for fluoropyrimidine response. Given its various biological functions in cancer progression, TP is a promising target in cancer treatment. Further translational research is required in this area.
AB - Thymidine phosphorylase (TP) is a nucleoside metabolism enzyme that plays an important role in the pyrimidine pathway.TP catalyzes the conversion of thymidine to thymine and 2-deoxy-α-D-ribose-1-phosphate (dRib-1-P). Although this reaction is reversible, the main metabolic function of TP is catabolic. TP is identical to the angiogenic factor platelet-derived endothelial-cell growth factor (PD-ECGF). TP is overexpressed in several human cancers in response to cellular stressful conditions like hypoxia, acidosis, chemotherapy and radiotherapy. TP has been shown to promote tumor angiogenesis, invasion, metastasis, evasion of the immune-response and resistance to apoptosis. Some of the biological effects of TP are dependent on its enzymatic activity, while others are mediated through cytokines like interleukin 10 (IL-10), basic fibroblast growth factor (bFGF) and tumour necrosis factor α (TNFα). Interestingly, TP also plays a role in cancer treatment through its role in the conversion of the oral fluoropyrimidine capecitabine into its active form 5-FU. TP is a predictive marker for fluoropyrimidine response. Given its various biological functions in cancer progression, TP is a promising target in cancer treatment. Further translational research is required in this area.
KW - Angiogenesis
KW - Hallmarks of cancer
KW - Predictive biomarkers
KW - Thymidine phosphorylase
UR - http://www.scopus.com/inward/record.url?scp=84939832459&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84939832459&partnerID=8YFLogxK
U2 - 10.1007/s12307-015-0173-y
DO - 10.1007/s12307-015-0173-y
M3 - Review article
C2 - 26298314
AN - SCOPUS:84939832459
SN - 1875-2292
VL - 9
SP - 33
EP - 43
JO - Cancer Microenvironment
JF - Cancer Microenvironment
IS - 1
ER -