Thiopurines: factors influencing toxicity and response.
Thiopurines are the backbone of current anti-leukemia regimens and have also been effective immunosuppressive agents for the past half a century. Extensive research on their mechanism of action has been undertaken, yet many issues remain to be addressed to resolve unexplained cases of thiopurine toxicity or treatment failure. The aim of this review is to summarize current knowledge of the mechanism of thiopurine action in experimental models and put into context with clinical observations. Clear understanding of their metabolism will contribute to maximizing efficacy and minimizing toxicity by individually tailoring therapy according to the expression profile of relevant factors involved in thiopurine activation pathway.
Fotoohi
Alan Kambiz
AK
Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, SE-17176 Stockholm, Sweden.
Coulthard
Sally A
SA
Albertioni
Freidoun
F
D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D015394:Molecular Structure; D011110:Polymorphism, Genetic; D011687:Purines / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D011687:Purines; D008780:Methyltransferases; C022745:thiopurine methyltransferase