Form Of Multidrug Resistance Research Articles

The endocytic receptor protein LRP-1 modulate P-glycoprotein mediated drug resistance in MCF-7 cells.

Multidrug resistance (MDR) is a major obstacle to successful cancer chemotherapy. A typical form of MDR is due to the overexpression of membrane transport proteins., such as Glycoprotein-P (P-gp), resulting in an increased drug efflux preventing drug cytotoxicity. P-gp is mainly localized on the plasma membrane; however, it can also be endocytosed resulting in the trafficking of P-gp in endoplasmic reticulum, Golgi, endosomes, and lysosomes. The lysosomal P-gp has been found to be capable of transporting and sequestering P-gp substrates (e.g., Doxorubicin (Dox)) into lysosomes to protect cells against cytotoxic drugs. Many translational studies have shown that low-density lipoprotein receptor-related protein-1 (LRP-1) is involved in endocytosis and regulation of signalling pathways. LRP-1 mediates the endocytosis of a diverse set of extracellular ligands that play important roles in tumor progression. Here, we investigated the involvement of LRP-1 in P-gp expression and subcellular redistribution from the cell surface to the lysosomal membrane by endocytosis and its potential implication in P-gp-mediated multidrug resistance in MCF-7 cells. Our results showed that MCF-7 resistant cells (MCF-7R) overexpressed the P-gp, LRP-1 and LAMP-1 and were 11.66-fold resistant to Dox. Our study also revealed that in MCF-7R cells, lysosomes were predominantly high density compared to sensitized cells and P-gp was localized in the plasma membrane and lysosomes. LRP-1 blockade reduced lysosomes density and level of LAMP-1 and P-gp. It also affected the subcellular distribution of P-gp. Under these conditions, we restored Dox nuclear uptake and ERK 1/2 activation thus leading to MCF-7R cell sensitization to Dox. Our data suggest that LRP-1 is able to modulate the P-gp expression and subcellular redistribution by endocytosis and to potentiate the P-gp-acquired Dox resistance.

First iron(II) organometallic compound acting as ABCB1 inhibitor

Five new iron (II) complexes bearing imidazole-based (Imi-R) ligands with the general formula [Fe(η5-C5H5)(CO)(PPh3)(Imi-R)][CF3SO3] were synthesized and fully characterized by several spectroscopic and analytical techniques. All compounds crystallize in centrosymmetric space groups in a typical “piano stool” distribution. Given the growing importance of finding alternatives to overcome different forms of multidrug resistance, all compounds were tested against cancer cell lines with different ABCB1 efflux pump expression, namely, the doxorubicin-sensitive (Colo205) and doxorubicin-resistant (Colo320) human colon adenocarcinoma cell lines. Compound 3 bearing 1-benzylimidazole was the most active in both cell lines with IC50 values of 1.26 ± 0.11 and 2.21 ± 0.26 μM, respectively, being also slightly selective against the cancer cells (vs. MRC5 normal human embryonic fibroblast cell lines). This compound, together with compound 2 bearing 1H-1,3-benzodiazole, were found to display very potent ABCB1 inhibitory effect. Compound 3 also showed the ability to induce cell apoptosis. Iron cellular accumulation studies by ICP-MS and ICP-OES methods revealed that the compounds’ cytotoxicity is not related to the extent of iron accumulation. Yet, it is worth mentioning that, from the compounds tested, 3 was the only one where iron accumulation was greater in the resistant cell line than in the sensitive one, validating the possible role of ABCB1 inhibition in its mechanism of action.

MP39-20 COST OF URINARY TRACT INFECTIONS WITH AND WITHOUT ANTIBIOTIC RESISTANCE IN THE UNITED STATES FROM 2012-2019

You have accessJournal of UrologyCME1 Apr 2023MP39-20 COST OF URINARY TRACT INFECTIONS WITH AND WITHOUT ANTIBIOTIC RESISTANCE IN THE UNITED STATES FROM 2012-2019 Meera Nagpal, Jacky Chu, and Amy Dobberfuhl Meera NagpalMeera Nagpal More articles by this author , Jacky ChuJacky Chu More articles by this author , and Amy DobberfuhlAmy Dobberfuhl More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003277.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urinary tract infections (UTI) are the second most common type of infection in older adults, and serious cases can lead to hospitalization, with severe complications like kidney failure and sepsis. Meanwhile, antibacterial resistance is on the rise, which can impact the severity of hospitalizations and clinical outcomes, as well as hospital costs. In this study, we explore the costs and characteristics associated with UTI hospitalizations with and without multi-drug resistance (MDR). METHODS: Using the Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS), a longitudinal database of inpatient visits in the United States (US), we conducted a retrospective study of UTI hospitalizations from 2012-2019. Among inpatient visits with UTI as a primary diagnosis, we further examined those with ICD-9 and ICD-10 codes of multi-drug resistance. Demographics associated with inpatient visits were collected, and hospital costs were inflation-adjusted to 2022 US dollars. In addition, we fitted a linear regression model on the variables of sex, race, payment type, length of stay, and age. RESULTS: From 2012 to 2019, the study found an approximately weighted estimate of 23,810 records of UTI hospitalizations, and among those, 595 (2.5%) records had some form of multi-drug resistance. Among UTI records, the mean cost was $7766 and the mean length of stay (LOS) was 4 days. Among UTI with MDR records, the mean cost was $9902 and the mean LOS was 4.8 days. The average cost of UTI hospitalizations increased by 10.2% from 2012 to 2019. Surprisingly, the cost of UTI hospitalizations in multi-drug resistant patients decreased by 45% over this time span. Results from the linear regression model from UTI inpatient visits show that lower costs were most strongly associated with White race (p<0.001), Black race (p<0.001), while higher costs were associated with Asian/Pacific Islander race (p<0.001) and LOS (p<0.001). The linear regression model from UTI with MDR records showed lower costs most robustly correlated with White race (p<0.05), while LOS (p<0.0001) and female sex (p<0.05) correlated with higher costs. CONCLUSIONS: This study found that mean cost of UTI inpatient visits was higher in those with MDR than no MDR. Overall costs have increased over time, and several demographics were associated with varying costs. Future studies should more closely examine the costs associated with MDR and more complicated sequelae of UTIs. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e544 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Meera Nagpal More articles by this author Jacky Chu More articles by this author Amy Dobberfuhl More articles by this author Expand All Advertisement PDF downloadLoading ...

Advanced diagnostic and therapeutic strategies in nanotechnology for lung cancer.

As a highly invasive thoracic malignancy with increasing prevalence, lung cancer is also the most lethal cancer worldwide due to the failure of effective early detection and the limitations of conventional therapeutic strategies for advanced-stage patients. Over the past few decades, nanotechnology has emerged as an important technique to obtain desired features by modifying and manipulating different objects on a molecular level and gained a lot of attention in many fields of medical applications. Studies have shown that in lung cancer, nanotechnology may be more effective and specific than traditional methods for detecting extracellular cancer biomarkers and cancer cells in vitro, as well as imaging cancer in vivo; Nanoscale drug delivery systems have developed rapidly to overcome various forms of multi-drug resistance and reduce detrimental side effects to normal tissues by targeting cancerous tissue precisely. There is no doubt that nanotechnology has the potential to enhance healthcare systems by simplifying and improving cancer diagnostics and treatment. Throughout this review, we summarize and highlight recent developments in nanotechnology applications for lung cancer in diagnosis and therapy. Moreover, the prospects and challenges in the translation of nanotechnology-based diagnostic and therapeutic methods into clinical applications are also discussed.

CD13: A Key Player in Multidrug Resistance in Cancer Chemotherapy.

Cancer is one of the most serious diseases that are harmful to human health. Systemic chemotherapy is an optimal therapeutic strategy for the treatment of cancer, but great difficulty has been encountered in its administration in the form of multidrug resistance (MDR). As an enzyme on the outer cell surface, CD13 is documented to be involved in the MDR development of tumor cells. In this review, we will focus on the role of CD13 in MDR generation based on the current evidence.

Antibiotics from Deep-Sea Microorganisms: Current Discoveries and Perspectives.

The increasing emergence of new forms of multidrug resistance among human pathogenic bacteria, coupled with the consequent increase of infectious diseases, urgently requires the discovery and development of novel antimicrobial drugs with new modes of action. Most of the antibiotics currently available on the market were obtained from terrestrial organisms or derived semisynthetically from fermentation products. The isolation of microorganisms from previously unexplored habitats may lead to the discovery of lead structures with antibiotic activity. The deep-sea environment is a unique habitat, and deep-sea microorganisms, because of their adaptation to this extreme environment, have the potential to produce novel secondary metabolites with potent biological activities. This review covers novel antibiotics isolated from deep-sea microorganisms. The chemical classes of the compounds, their bioactivities, and the sources of organisms are outlined. Furthermore, the authors report recent advances in techniques and strategies for the exploitation of deep-sea microorganisms.

Oligodynamic Effect of Silver Nanoparticles: a Review

The advent, efficacy, followed by the undiscerning and unrestricted consumption of antibiotics resulted in undue evolution in microbes in the form of multidrug resistance eventually resulting in the cultivation of new challenges to develop the new-generation antimicrobial therapy. A critical need for the development of novel, broad-spectrum therapeutics has thus arrived. The Silver nanoparticles (AgNPs) over the last few years have gained immense reputation as the next-generation antibiotics owing to their broad-spectrum activity against the disease-causing microbes which has been also extended against the highly evolved MDR strains. Also known to support the synergistic effect in combination with various commercially used antibiotics, the potential of AgNPs could be extensively exploited to gradually replace the old-generation drugs that certainly have lost their tooth against the resistant microbes.

Backbone assignment of the apo-form of the human C-terminal domain of UDP-glucuronosyltransferase 1A (UGT1A).

A major component of phase II drug metabolism is the covalent addition of glucuronic acid to metabolites and xenobiotics. This activity is carried out by UDP-glucuronosyltransferases (UGT) which bind the UDP-glucuronic acid donor and catalyze the covalent addition of glucuronic acid sugar moieties onto a wide variety of substrates. UGTs play important roles in drug detoxification and were recently shown to act in an inducible form of multi-drug resistance in cancer patients. Despite their biological importance, structural understanding of these enzymes is limited. The C-terminal domain is identical for all UGT1A family members and required for binding to UDP-glucuronic acid as well as involved in contacts with substrates. Here, we report the backbone assignments for the C-terminal domain of UGT1A. These assignments are a critical tool for the development of a deeper biochemical understanding of substrate specificity and enzymatic activity.

Molecular Pathways: GLI1-Induced Drug Glucuronidation in Resistant Cancer Cells.

Drug resistance remains a major impediment in the development of durable cancer therapies. Studies in acute myelogenous leukemia (AML) patients revealed a new form of multidrug resistance. Here, increased glioma-associated protein GLI1 leads to elevation of the UDP-glucuronosyl transferase (UGT) enzymes. UGTs add glucuronic acid to xenobiotics and metabolites. Traditionally, the loss of these enzymes is thought to contribute to cancer as a result of impaired clearance of environmental carcinogens. However, we demonstrate that overexpression of UGTs can contribute to oncogenesis by promoting drug resistance. Indeed, UGT levels in AML patients treated with ribavirin and/or cytarabine were elevated at relapse relative to diagnosis. This was reversed by GLI1 inhibition, suggesting a clinically relevant strategy to overcome drug resistance. Further, overexpression of UGTs can also lead to drug resistance in other cancers, such as certain Hsp90 inhibitors and vorinostat in colorectal and chronic lymphoblastic leukemia, respectively. Not all drugs are targets of glucuronidation, suggesting that UGT status could be relevant to treatment choice. Here, we describe several facets of UGT biology and how these could be exploited clinically. These studies demonstrate how drugs in cancer cells can be metabolized differentially than their normal counterparts. In summary, we describe a new form of drug resistance relevant to a variety of cancer contexts.

When will resistance be futile?

Cancer cells rapidly evolve a multitude of defense mechanisms to evade the effects of the oncologist's drug arsenal. Unfortunately, clinical strategies to overcome these lag far behind. This mismatch likely underlies our inability to implement new durable treatment strategies. Here, a new form of multidrug resistance, inducible drug glucuronidation, is discussed. This form was discovered while developing means to target a specific oncogene, the eukaryotic translation initiation factor 4E (eIF4E), with its inhibitor ribavirin. In two clinical studies, ribavirin treatment led to substantial clinical responses, but all responding patients eventually relapsed. In most cases, this was due to the overexpression of the sonic hedgehog transcription factor Gli1, which elevated the UDP glucuronsyltransferase UGT1A enzymes. UGT1As add glucuronic acid to many drugs. Indeed, these cells are resistant to not only ribavirin, but also Ara-C, and likely other drugs. Inhibition of Gli1 reduced UGT1As, eliminated drug glucuronides, and renewed sensitivity to ribavirin and Ara-C. These studies highlight that cancer cells and their resistant counterparts metabolize drugs differently from each other as well as from normal cells. Likely, these inducible modifications go beyond glucuronidation. Understanding the extent of inducible drug modifications and the pathways that drive expression of the corresponding enzymatic machinery will better position us to finally make resistance futile.

Inducible drug modification: A new form of resistance

Inducible drug modification: A new form of resistance

Bacteriophages in &amp;lt;i&amp;gt;Escherichia coli&amp;lt;/i&amp;gt; antimicrobial resistance

The continuous battle between humans and the multitude of pathogenic microorganisms in the environment has sought relief in the form of antimicrobials. But the counter attack by pathogenic organisms in the form of multidrug resistance, acquired by various mechanisms such as transformation, transposition, conjugation and transduction is a major reason for concern. Bacteriophages have contributed in a significant way to dissemination of genes encoding antimicrobial resistance, heavy metal resistance and virulence factors through the phenomenon of transduction. This review aims at compiling information about the different mechanisms by which bacteriophages aid in transferring genes involved in antimicrobial resistance to Escherischia coli in various environments.

Regulation Exerted by miRNAs in the Promoter and UTR Sequences:MDR1/P-gp Expression as a Particular Case

One of the common forms of multidrug resistance (MDR) is caused by activation of the mdr1 (ABCB1) gene, resulting in overexpression of P-glycoprotein (P-gp) and conferring cancer cell resistance to a broad range of chemotherapeutics. Recently, P-gp-mediated MDR has been associated with aberrant expression of microRNAs (miRNAs) in several types of cancer. miRNAs are small noncoding RNAs that regulate gene expression in a posttranscriptional manner through partial or total hybridization with specific sequences in the 3'-UTR of target mRNAs. Interestingly, there are at least two reports that suggest an additional regulation by miRNAs at the mdr1 promoter level. Here, we critically analyzed some of the miRNAs that regulate P-gp expression at two different levels: posttranscriptional and transcriptional. We proposed that the latter may occur through two possible scenarios: (1) direct miRNA hybridization with an active promoter and (2) triplex structure formation (double-stranded DNA/RNA) stabilized by Argonaute 2. Also, we classified transcriptional gene silencing (1) by homology, represented by small interfering RNAs directed to viral promoters, and (2) by complementarity (Watson-Crick/Hoogsteen base pairing), mediated by miRNAs. Transcriptional regulation could represent a new avenue of knowledge applicable to the modulation of other genes mediated by these noncoding RNAs.

Different Modalities of Intercellular Membrane Exchanges Mediate Cell-to-cell P-glycoprotein Transfers in MCF-7 Breast Cancer Cells

Multi-drug resistance (MDR) is a phenomenon by which tumor cells exhibit resistance to a variety of chemically unrelated chemotherapeutic drugs. The classical form of multidrug resistance is connected to overexpression of membrane P-glycoprotein (P-gp), which acts as an energy dependent drug efflux pump. P-glycoprotein expression is known to be controlled by genetic and epigenetic mechanisms. Until now processes of P-gp gene up-regulation and resistant cell selection were considered sufficient to explain the emergence of MDR phenotype within a cell population. Recently, however, "non-genetic" acquisitions of MDR by cell-to-cell P-gp transfers have been pointed out. In the present study we show that intercellular transfers of functional P-gp occur by two different but complementary modalities through donor-recipient cells interactions in the absence of drug selection pressure. P-glycoprotein and drug efflux activity transfers were followed over 7 days by confocal microscopy and flow cytometry in drug-sensitive parental MCF-7 breast cancer cells co-cultured with P-gp overexpressing resistant variants. An early process of remote transfer was established based on the release and binding of P-gp-containing microparticles. Microparticle-mediated transfers were detected after only 4 h of incubation. We also identify an alternative mode of transfer by contact, consisting of cell-to-cell P-gp trafficking by tunneling nanotubes bridging neighboring cells. Our findings supply new mechanistic evidences for the extragenetic emergence of MDR in cancer cells and indicate that new treatment strategies designed to overcome MDR may include inhibition of both microparticles and Tunneling nanotube-mediated intercellular P-gp transfers.

Peroxisome proliferator-activated receptors in regulation of cytochromes P450: new way to overcome multidrug resistance?

Embryonic and tumour cells are able to protect themselves against various harmful compounds. In human pathology, this phenomenon exists in the form of multidrug resistance (MDR) that significantly deteriorates success of anticancer treatment. Cytochromes P450 (CYPs) play one of the key roles in the xenobiotic metabolism. CYP expression could contribute to resistance of cancer cells to chemotherapy. CYP epoxygenases (CYP2C and CYP2J) metabolize about 20% of clinically important drugs. Besides of drug metabolism, CYP epoxygenases and their metabolites play important role in embryos, normal body function, and tumors. They participate in angiogenesis, mitogenesis, and cell signaling. It was found that CYP epoxygenases are affected by peroxisome proliferator-activated receptor α (PPARα). Based on the results of current studies, we assume that PPARs ligands may regulate CYP2C and CYP2J and in some extent they may contribute to overcoming of MDR in patients with different types of tumours.

Multidrug resistance gene expression and ABCB1 SNPs in plasma cell myeloma

Multi-drug resistance (MDR) leads to impaired treatment efficacy in all forms of malignancy. The main forms of MDR are thought to be mediated by the substrate transporting actions of certain adenosine triphosphate binding cassette (ABC) transport proteins. The genes ABCB1, ABCB4, ABCC1, ABCG2 and LRP1 have been identified as the most prominent contributors to clinically significant MDR. To date, no study has investigated the expression of these genes in plasma cell myeloma (PCM), or attempted to relate their expression to the incidence of relapse and/or stage at presentation. Here, we show that ABCB4 may be a prominent mediator of tumour cell MDR within PCM. Additionally, there are three SNPs (rs1045642, rs2032582 and rs1128503) within the most widely studied of these genes, ABCB1, which have been suggested to have a potential impact on OS in PCM and which may form a haplotype in ABCB1. rs1045642 in ABCB1 appears to be the only SNP affecting OS within the PCM patients studied, with minimal linkage disequilibrium demonstrated between it and rs2032582 and rs1128503.

Reversal of multidrug resistance by small interfering RNA (siRNA) in doxorubicin-resistant MCF-7 breast cancer cells

Purpose Resistance to anticancer drugs is a serious obstacle to cancer chemotherapy. A common form of multidrug resistance (MDR) is caused by the overexpression of transmembrane transporter proteins P-glycoprotein (P-gp) and multidrug resistance-associated protein-1 (MRP1), encoded by MDR1 and MRP1 genes, respectively. These proteins lead to reduced intracellular drug concentration and decreased cytotoxicity by means of their ability to pump the drugs out of the cells. Breast cancer tumor resistance is mainly associated with overexpression of P-gp/MDR1. Although some chemical MDR modulators aim to overcome MDR by interfering functioning of P-gp, their toxicities limit their usage in clinics. Consequently, RNA interference mediated sequence specific inhibition of the expression of P-gp/MDR1 mRNA may be an efficient tool to reverse MDR phenotype and increase the success of chemotherapy. Aim of this study was resensitizing doxorubicin-resistant breast cancer cells to anticancer agent doxorubicin by selective downregulation of P-gp/MDR1 mRNA. Methods The effect of the selected MDR1 siRNA, and MRP1 expression after MDR1 silencing was determined by qPCR analysis. Intracellular drug accumulation and localization was investigated by confocal laser scanning microscopy after treatment with MDR1 siRNA. XTT cell proliferation assay was performed to determine the effect of MDR1 silencing on doxorubicin sensitivity. Results The results demonstrated that approximately 90% gene silencing occurred by the selected siRNA targeting MDR1 mRNA. However, the level of MRP1 mRNA did not change after MDR1 downregulation. Silencing of P-gp encoding MDR1 gene resulted in almost complete restoration of the intracellular doxorubicin accumulation and relocalization of the drug in the nuclei. Introduction of siRNA resulted in about 70% resensitization to doxorubicin. Conclusions Selected siRNA duplex was shown to effectively inhibit MDR1 gene expression, restore doxorubicin accumulation and localization, and enhance chemosensitivity of resistant cells, which makes it a suitable candidate for therapeutic applications.

The Na +/K +-ATPase is the Achilles Heel of multi-drug-resistant cancer cells

We recently reported that over-expressed Na +/K +-ATPase α subunits are new important anti-cancer targets. Cardiotonic steroids are the natural ligands of Na +/K +-ATPase and thus potentially potent anti-cancer agents with a novel mechanism of action. We report here that the hemi-synthetic cardenolide 19-hydroxy-2″oxovoruscharin is impressively active in cancer cells expressing diverse forms of multi-drug resistance (MDR) either conferred by the over-expression of selected drug-transporter proteins or induced by a range of chemotherapeutic agents. Together with the inability of tumor cells to acquire resistance to 19-hydroxy-2″oxovoruscharin, our data suggest that this novel compound could be especially applicable to notoriously drug-resistant cancers.

Antiproliferative activity of ent-abietane lactones against resistant human cancer cell lines

Multidrug resistance (MDR) is considered to be one of the main causes of chemotherapy failure. The mechanisms of MDR could be related with the intracellular drug distribution through overexpression of certain transport proteins (e.g. Pgp/MDR1). This type of MDR is often known as classical or typical MDR. However, it does not completely explain the phenomenon. Alternative forms of MDR have been described, known as atypical MDR that included, among others, the change in drug targets (e.g. decreased activity of Topoisomerase II) [1]. Topoisomerases are nuclear enzymes that are essential for DNA replication, transcription, chromosomal aggregation and DNA recombination. For these reasons, Topo II is one of the possible targets for the commonly used anticancer drugs [2]. The aim of this work was to study the antiproliferative effect of several ent-abietane diterpenic lactones, isolated from Euphorbia tuckeyana, in human cancer cell lines, which were derived from three different tumour entities: gastric (EPG85–257), pancreatic (EPP85–181) and colon (HT-29) carcinomas. The classical and atypical MDR sublines of these cell models were also investigated. IC50 values were determined by proliferation assays, after continuous exposure for 5 days. Relative resistance (RR) was also determined as the relation between the IC50 of the resistance cell line and the IC50 of the parental drug-sensitive cell line. In parental drug sensitive cell lines, all the tested compounds showed a weak antiproliferative effect. However, most of the drug resistant cancer sublines showed increased sensitivities to the studied compounds when compared to the parental sublines. Some of the tested compounds were found to be highly effective against the classical MDR subline of gastric carcinoma, showing RR of 0.08 and 0.09. The results obtained lead to conclude that, ent-abietane lactones may be considered as potential new drugs for the treatment of drug-resistant human cancer cells.

Drug Resistance in Renal Tumors of Childhood

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.