Abstract
Purine nucleoside phosphorylase (PNP) is an important catalytic enzyme in the purine salvage pathway; its deficiency is associated with T-cell lymphopenia and with humoral deficiency. This clinical observation led to the investigation of PNP inhibitors and their possible clinical application in the management of hematologic malignancies, notably those of T-cell lineage. Forodesine is the most potent of the PNP inhibitors. Its effect appears to be linked to increased 2́-deoxyguanosine levels in plasma, which in turn is converted to 2́-deoxyguanosine triphosphate in target cells and disrupts DNA synthesis. Several preclinical studies have shown forodesines effect against lymphocytes in vitro and in vivo, and these findings have led to several Phase I/II studies in patients with lymphoid neoplasms. Early clinical trials show that forodesine has promise as a single agent for the treatment of relapsed/refractory hematologic malignancies, and combination therapies might be warranted to improve clinical results.
Original language | English (US) |
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Pages (from-to) | 1211-1217 |
Number of pages | 7 |
Journal | Future Oncology |
Volume | 6 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2010 |
Keywords
- acute lymphoblastic leukemia
- chronic lymphocytic leukemia
- cutaneous T-cell lymphoma
- forodesine
ASJC Scopus subject areas
- Oncology
- Cancer Research