Drug Resistance in Renal Tumors of Childhood

Cheppail      Ramachandran

Abstract

Renal cancers are as one of the most common drug resistant neoplasms affecting children and multidrug resistance (MDR) happened to be an important reason for the failure of chemotherapy in refractory cancers of childhood. MDR can be intrinsic or acquired, depending on the time of its occurrence, either at diagnosis or during chemotherapy. Renal cancers often have intrinsic form of MDR because of de novo expression of P-glycoprotein (P-gp) in renal cells. Molecular investigations on MDR during the past two decades have led to the isolation and characterization of genes coding for P-gp, multidrug resistance-associated protein (MRP), lung resistance-related protein (LRP), breast cancer resistance protein (BCRP/MXR), drug resistance-associated protein (DRP), and ATP-binding cassette protein (ABCP). Several molecular probes, primer pairs, and monoclonal antibodies have been developed over the years to quantify the regulation and expression of these drug resistance markers in tumor cells. Methodologies have also been standardized to estimate the gene amplification, mRNA and protein expression, and functionality of drug resistance proteins in clinical specimens from cancer patients. Because of the recent developments in microarray technology, DNA and protein arrays against drug resistant genes are available commercially now. This review includes techniques for detection and quantification of the expression and function of these drug resistance genes in childhood renal tumors. Since these markers have clinical significance, currently available technology warrants the application of these markers in clinical oncology. Moreover, the first, second and third generation drug resistance modifiers have been developed over the past several years for overcoming drug resistance problem in tumor cells. Unfortunately, these reversing agents are yet to be proved successful clinically. Since treatment protocols are usually adopted from adult tumor patients into childhood population, clinical trials with modifying agents are yet to be undertaken and/or concluded in pediatric renal cancer patients. More clinical studies may be required to analyze the genes involved in the MDR of childhood renal cancer patients and trials have to be undertaken to evaluate the efficacy of MDR modifying agents in them, at least in parallel with adult patients.

Keywords: Childhood renal tumor, multidrug resistance, chemotherapy, molecular diagnosis, functional assay, resistance modifiers

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