Collection of Blood, Bone Marrow, Tumor, or Tissue Samples From Patients With Cancer to Study Drug Resistance

Overview

This study will examine blood, bone marrow, tumor and tissue samples from patients with cancer to study tumor resistance to chemotherapy (drug treatment). Many patients with cancer improve initially with chemotherapy, but then have a disease relapse, after which their tumor no longer responds to treatment. Other patients tumors are drug-resistant from the start. The study will look for "resistance factors"-substances in blood and tissues that render tumors resistant to chemotherapy. The findings may provide information needed to develop methods of combating drug resistance. Patients with cancer who are 18 years or older may be eligible for this study. Participants will have 40 milliliters (3 tablespoons) of blood drawn at the beginning of the study; additional samples will be obtained periodically during the course of treatment. A small sample of tumor or normal tissue will be taken from patients who undergo surgery or tumor biopsy (removal of a small piece of tumor) for medical reasons or as part of a research treatment protocol. Patients who do not require surgery or biopsy may be asked permission to obtain a tumor sample. Depending on the location of the tumor, this may be done by: 1) withdrawing bone marrow through a small needle; 2) removing fluid from the chest or abdomen; 3) removing a small tumor sample through a needle; or 4) removing the sample with a small incision into or around the tumor. These procedures will be done only if they are of low risk to the patient.

Background: Ongoing research in the Molecular Pharmacology Section, NCI, requires the availability of blood, fluid, bone marrow, tumor, hair follicle and tissue samples from patients with cancer. Resistance is the underlying cause of treatment failure, and may present as acquired or intrinsic drug resistance. Patients with cancer frequently present with chemotherapy-responsive disease, and undergo tumor response, only to eventually experience relapse, at which time the tumor may be refractory to further treatment. This is termed acquired drug resistance; while intrinsic resistance implies a cancer that is refractory from the outset. Diverse mechanisms of drug resistance have been described and are often dependent upon the particular drug under study. Objectives: To obtain blood, fluid, hair follicles, bone marrow, tumor and/or normal tissue samples that would allow development of assays for use in subsequent clinical trials. Eligibility: Patients with a prior diagnosis of malignancy, with advanced or refractory cancer will be evaluated in the GMB Clinic, NCI. Participants may be on, or in the process of being evaluated for a research protocol. Participants may receive treatment on the standard care protocol. Normal volunteers may enroll in the study. Design: Acquired samples will be recorded in the computerized data bank currently existing in the Molecular Pharmacology Section. No germline testing will be performed on any of the samples collected. Tests will be pilot studies relating to the Section s work on the biology of drug resistance and cell survival in cancer. Sample collection for patients with cancer: * Blood samples, fluid samples, or hair follicle samples may be collected at the initial visit, and at follow up visits. * Tumor samples may be obtained by fine needle aspirate, by removal of pleural or peritoneal fluid, or by excisional biopsy, providing the tumor is accessible. * Bone marrow aspirate, thoracentesis, and paracentesis may be performed. Normal volunteers may enroll in the study for collection of blood, fluid, and/or hair follicle samples. Examples of the types of studies to be performed with biopsies will be drug resistance gene expression assays, with the goal of demonstrating the utility of the assay in participant samples. Evaluation of methods to detect drug resistance proteins and genes will be explored, including Northern blot, immunoblot, polymerase chain reaction assay, and RNA in situ hybridization. With whole blood, we may evaluate the presence of dye transport in an ex vivo assay, for example, using inhibitors of ABCG2. Evidence of drug accumulation or DNA damage may be sought in participant mononuclear cells or in hair follicle samples.