Journal
MEDICINAL RESEARCH REVIEWS
Volume 29, Issue 6, Pages 903-953Publisher
WILEY
DOI: 10.1002/med.20159
Keywords
thymidine phosphorylase (TP); angiogenesis; cancer chemotherapy; fluoropyrimidines; thymidine phosphorylase inhibitors
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Funding
- Centers of Excellence of the K.U. Leuven [05/15]
- Geconcerteerde Onderzoeksacties of the K.U. Leuven [GOA 05/19]
- Comision Interministerial de Ciencia y Tecnologia [SAF2006-12713-C02]
- Comunidad de Madrid [S-BIO/0214/2006]
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Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor (PD-ECGF), is ail enzyme, which is upregulated in a wide variety of solid tumors including breast and colorectal cancers. TP promotes tumor growth and metastasis by preventing apoptosis and inducing angiogenesis. Elevated levels of TP are associated with tumor aggressiveness and poor prognosis. Therefore, TP inhibitors are synthesized in an attempt to prevent tumor angiogenesis and metastasis. TP is also indispensable for the activation of the extensively used 5-fluorouracil prodrug capecitabine, which is clinically used for the treatment of colon and breast cancer. Clinical trials that combine capecitabine with TP-inducing therapies (such as taxanes or radiotherapy) suggest that increasing TP expression is an adequate strategy to enhance the antitumoral efficacy of capecitabine. Thus, TP plays a dual role in cancer development and therapy: on the one hand, TP inhibitors can abrogate the tumorigenic and metastatic properties of TP; on the other, TP activity is necessary for the activation of several chemotherapeutic drugs. This duality illustrates the complexity of the role of TP in tumor progression and in the clinical response to fluoropyrimidine-based chemotherapy. (C) 2009 Wiley Periodicals, Inc. Med Res Rev, 29, No. 6, 903-953, 2009
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