Abstract
Imatinib is a common therapy in
the clinical management of chronic myeloid leukemia (CML). Imatinib, a member
of the family of tyrosine kinase inhibitors, is a drug transporter subtrate. It
binds expansively to plasma proteins, and can inhibit its own transporters and
metabolizing enzymes. The strongest drawback to imatinib treatment is
resistance to such a treatment. Even tough response rates are high in imatinib
treatment, 70-90% of the patients may manifest nonresponse or disease
progression. This observed resistance may be a result of genetic mutations or
gene amplifications of drug targets. Cancer cells can develop resistance
towards one one drug, to a group of cytotoxic agents or to a number of drugs
which are not from the same therapeutic group. There are other resistance
mechanisms associated with MDR. One of the fundamental resistance mechanisms in
CML patients is mutations in the BCR-ABL1 tyrosine kinase region. However,
imatinib resistance may develop independently in some patients. The reason why
is the presence of additional factors required for formation of a completely
drug resistant phenotype. BCR-ABL positive cells increase the activity of the
GLUT 1 glucose transporter thus increase glucose intake. Classical dose regimen
during imatinib treatment has revealed differences going up to 4-fold. Drug
plasma level determination, and analysis of the impact of transporter protein
polymorphic variants on drug levels in CML patients who are receiving imatinib
treatment, clinical evaluation of the effects of polymorphisms on imatinib
efficacy and resistance development will help enlighten the individual
mechanisms behind interindividual differences in imatinib pharmacokinetics.
References
- Pelin KILIÇ
- Turkish Medicines and Medical Devices Agency
Abstract
References
- Pelin KILIÇ
- Turkish Medicines and Medical Devices Agency
Details
| Journal Section | Articles |
|---|---|
| Authors | |
| Publication Date | February 16, 2017 |
| Published in Issue | Year 2017 Volume: Volume 2 Issue: İssue 1 (1) - 2.İnternational Congress Of Forensic Toxicology |
