Multidrug Resistance Molecular Target Analysis of Human Samples Collected in Clinical Trials Performed Outside of the Intramural National Cancer Institute

Brief Summary

Detailed Description

Background: Ultimately, patients who succumb to cancer do so because of drug resistance. Mechanisms of drug resistance have been explored in the laboratory and in clinical samples for some time, yet the prevailing cause of drug resistance, if indeed there is a single cause, is not known. One mechanism of drug resistance is multidrug efflux, mediated by P-glycoprotein. Other mechanisms have been proposed. Our laboratory has expertise in the analysis of drug transporter expression and activity in clinical samples. Objectives: To determine expression of P-glycoprotein and other multidrug transporters thought to mediate clinical drug resistance. To evaluate inhibition of P-glycoprotein and other multidrug transporters through assessment of efflux activity in cells obtained from patients enrolled on clinical trials at other institutions. To identify and evaluate mechanisms of drug resistance using molecular assays such as cDNA array, real-time PCR analysis, and immunohistochemistry. Eligibility: Patients enrolled on clinical trials outside the NCI, and giving informed consent to the use of blood, tissue, or tumor samples for evaluation of mechanisms of drug resistance or evaluation of inhibition of multi-drug efflux. Future collaborations for similar studies will be added via the protocol amendment procedure; molecular studies other than ABC transporter assays will be added via the protocol amendment procedure. Design: Human tumor biopsies or blood samples will be collected from cancer patients enrolled on approved clinical trials, in accordance with the local protocol. These trials are being conducted at outside institutions, and the samples will be sent to the NCI for immunohistochemical analysis, cDNA array, PCR analysis, or for blood assays for detection of P-glycoprotein inhibition.

Primary Outcomes