Thymidine phosphorylase: a two-face Janus in anticancer chemotherapy

Area of Science:

• Biochemistry
• Oncology
• Molecular Biology

Background:

• Cytokines and growth factors regulate angiogenesis via paracrine or autocrine signaling.
• Platelet-derived endothelial cell growth factor (PD-ECGF) is highly expressed in tumors and stimulates endothelial cell migration, promoting angiogenesis.
• PD-ECGF is identical to thymidine phosphorylase (TP), an enzyme involved in thymidine metabolism.

Purpose of the Study:

• To review thymidine phosphorylase (TP), its activity, mechanisms, and role in angiogenesis.
• To discuss TP as a dual-target for controlling tumor-dependent angiogenesis.
• To highlight the design and biological characterization of novel TP inhibitors with anticancer potential.

Main Methods:

• Literature review of studies on PD-ECGF/TP and angiogenesis.
• Analysis of TP's role in tumor-specific expression and substrate specificity.
• Examination of TP inhibitors' design and biological characterization.

Main Results:

• PD-ECGF's angiogenic activity is attributed to its TP enzyme function, making 'PD-ECGF' a misnomer.
• TP's high tumor expression and broad substrate specificity suggest its use in activating anticancer agents.
• TP's angiogenic activity necessitates the development of specific inhibitors.

Conclusions:

• TP is a critical target for anticancer strategies, offering a dual approach.
• Inhibitors targeting TP's angiogenic activity show promising anticancer effects.
• Further research into TP inhibitors could lead to novel cancer therapies.