1. Predicting benefit from imatinib: are we close?
- Author
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Mitul Gandhi and Virginia G. Kaklamani
- Subjects
Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,ATP Binding Cassette Transporter, Subfamily B ,medicine.drug_class ,Pharmacology ,Polymorphism, Single Nucleotide ,Piperazines ,Tyrosine-kinase inhibitor ,Therapeutic index ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Sunitinib ,business.industry ,Organic Cation Transporter 1 ,Imatinib ,Hematology ,medicine.disease ,Clear cell renal cell carcinoma ,Pyrimidines ,Tolerability ,Pharmacogenomics ,Benzamides ,Female ,business ,medicine.drug ,Chronic myelogenous leukemia - Abstract
Th e treatment of chronic myelogenous leukemia (CML) was revolutionized with the introduction of the tyrosine kinase inhibitor (TKI) imatinib [1], off ering the prospect of highly eff ective therapy predicated upon targeting of specifi c molecularly defi ned aberrations. While second-generation TKIs appear to more frequently achieve major molecular response (MMR) [2], overall survival is not conclusively better, and imatinib remains an important and widely used agent in CML. Ideally, biological and genetic factors would identify those patients who will or are unlikely to derive benefi t from imatinib, and assist in informing the appropriate therapeutic dose. Such a pharmacogenomic approach to therapy has been explored in other several disease sites. For example, single nucleotide polymorphisms (SNPs) in VEGFR3 and CYP3A5 * 1 have been shown to predict lack of effi cacy and tolerability in patients with clear cell renal cell carcinoma (RCC) treated with sunitinib [3]. Similarly, mutations in CYP1A1 and FLT have also been shown to help predict toxicity with anti
- Published
- 2014