Role of Gene Variation in Effectiveness of Gleevec Treatment
This study will examine DNA from cancer patients previously treated with Gleevec to look for a variation (mutation) of the ABCG2 gene that may render the drug less effective in certain patients. Gleevec is used to treat chronic myeloid leukemia and gastrointestinal tumors. Although most patients respond to treatment, many with advanced disease develop resistance to the drug. It is thought that in some patients this resistance results from the action of a protein that causes Gleevec to be pumped out of the cells, reducing its usefulness.
Patients enrolled in clinical trials of Gleevec at the National Cancer Institute and at other participating institutions are eligible for this study.
DNA from patients' blood samples are analyzed for the ABCG2 gene and correlated with clinical data, such as the patient's age, race, disease state, weight, height, and body surface area. It will also look at the drug dose, how often the drug is given, the duration of treatment, side effects and other medications taken.
|Official Title:||Analysis of ABCG2 Genotype in Gleevec Treated Cancer Patients to Assess the Association of a Single Nucleotide Polymorphism (C421A) in ABCG2 and Response to Treatment|
|Study Start Date:||January 2005|
|Study Completion Date:||October 2008|
ABCG2, also known as breast cancer resistance protein (BCRP), is an ATP-binding cassette (ABC) transporter that has been shown to confer resistance to several drugs, including mitoxantrone and topotecan. Gleevec (imatinib mesylate) has recently been identified as a substrate for ABCG2. The expression of ABCG2 in the human jejunum has been shown to be higher than expression MDR1, which encodes for P-glycoprotein. Therefore, it is plausible that the oral bioavailability of Gleevec could be dependent on the extent of transport. A single nucleotide polymorphism (C421A) has been identified in ABCG2 and has been shown in vitro to result in functional inactivation of this transporter protein. In this study, the relationship between the genotypes of ABCG2 and the pharmacokinetics or side effects will be retrospectively explored in patients with cancer who had been previously enrolled on clinical trials of Gleevec.
|United States, District of Columbia|
|Washington Hospital Center|
|Washington, District of Columbia, United States, 20010|
|Katholieke Universiteit Leuven, U Hospitals UZ Gasthuisberg|