Pyrimidine and purine analogues, effects on cell cycle regulation and the role of cell cycle inhibitors to enhance their cytotoxicity.
In anti-cancer treatment, deoxynucleoside analogues are widely used in combination chemotherapy. Improvement can be achieved by rational design of novel combinations with cell cycle inhibitors. These compounds inhibit protein kinases, preventing the cell cycle from continuing when affected by deoxynucleoside analogs. The efficacy is dependent on the site of cell cycle inhibition, whether multiple cyclin-dependent kinases are inhibited and whether the inhibitors should be given before or after the deoxynucleoside analogs. The action of cell cycle inhibition in vivo may be limited by unfavorable pharmacokinetics. Preclinical and clinical studies will be discussed, aiming to design improved future strategies.
Sigmond
Jennifer
J
Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
Peters
Godfridus J
GJ
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004341:Drug Evaluation; D006801:Humans; D011687:Purines / Q000493:pharmacokinetics / Q000494:pharmacology*; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000494:pharmacology*
D011687:Purines; D011743:Pyrimidines; D018844:Cyclin-Dependent Kinases; C030986:pyrimidine; C030985:purine