Translocation of Nucleoside Analogs Across the Plasma Membrane in Hematologic Malignancies
| Autor: | Paula Fernández-Calotti, Marçal Pastor-Anglada, Dolors Colomer |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Chronic lymphocytic leukemia
Cell Antineoplastic Agents Nucleoside Transport Proteins Pharmacology Biochemistry Genetics medicine Animals Humans Nucleoside analogue Chemistry Cell Membrane Biological Transport Nucleosides Equilibrative nucleoside transporter Transporter General Medicine medicine.disease medicine.anatomical_structure Apoptosis Hematologic Neoplasms Molecular Medicine Efflux Nucleoside medicine.drug |
| Zdroj: | Nucleosides, Nucleotides and Nucleic Acids. 30:1324-1340 |
| ISSN: | 1532-2335 1525-7770 |
| Popis: | Nucleoside analogs are currently used in the treatment of various hematologic malignancies due to their ability to induce apoptosis of lymphoid cells. For nucleoside-derived drugs to exert their action, they must enter cells via nucleoside transporters from two gene families, SLC28 and SLC29 (CNT and ENT, respectively). Once inside the cell, these drugs must be phosphorylated to their active forms. In contrast, some members of the ATP-binding cassette (ABC) protein family have been identified as responsible for the efflux of the phosphorylated forms of these nucleoside-derived drugs. Here, we review the main nucleoside analogs used in hematologic malignancies and focus especially on those that are currently used in chronic lymphocytic leukemia (CLL). Moreover, we discuss the pharmacological profile of the nucleoside transporters, which determines the bioavailability of and cell sensitivity to these nucleoside-derived drugs. We also discuss the expression of nucleoside transporters and their activities in CLL as well as the possibility of modulating these transporter activities as a means of modulating intracellular drug availability and, consequently, responsiveness to therapy. |
| Databáze: | OpenAIRE |
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