Collection of Tissue Samples for Study of Multidrug Resistance

Overview

Background: Resistance to cancer chemotherapy develops in patients, rendering certain treatments ineffective. Despite much research, the prevailing cause of drug resistance is not known. One mechanism for drug resistance involves a protein called P-glycoprotein, or Pgp, which reduces the effectiveness of cancer treatments by "pumping" anti-cancer drugs out of tumor cells where they are supposed to work against the disease. Objectives: To identify and evaluate more thoroughly the roles of Pgp and other substances in mediating drug resistance. Eligibility: Patients enrolled in clinical trials of cancer therapies at the Children's Hospital of Pittsburgh; Cancer Centers of Carolinas; Arizona Clinical Research Center; University of Copenhagen; and Herlev Hospital, Copenhagen who have consented to the use of blood, tissue, or tumor samples for laboratory studies. Design: Blood, tumor, and tissue samples are collected from participants and sent to the NCI for various laboratory analyses. ...

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.