Cancer multidrug resistance

Persidis, Aris

doi:10.1038/5289

Cited by 292 publications

(226 citation statements)

References 14 publications

(4 reference statements)

Supporting

Mentioning

216

Contrasting

Unclassified

Order By: Relevance

“…Chemotherapy is the primary treatment for most patients, but one severe clinical problem that often causes failure of chemotherapy is multiple drug resistance (MDR) [2]. For decades, numerous studies have been performed on MDR of gastric cancer and several systems such as ATP-binding cassette (ABC) transporters, glutathione-S transferases and topoisomerases have been found to be involved in this malignant phenotype.…”

Section: Introductionmentioning

confidence: 99%

In-depth research of multidrug resistance related cell surface glycoproteome in gastric cancer

Li¹,

Sun²,

Zheng³

et al. 2013

Journal of Proteomics

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

In-depth research of multidrug resistance related cell surface glycoproteome in gastric cancer

Li¹,

Sun²,

Zheng³

et al. 2013

Journal of Proteomics

View full text Add to dashboard Cite

“…The prevailing medical dogma of cancer chemotherapy resistance is the overexpression of P-gp (MDR) [120][121][122][123][124] which is a very narrow perspective. Cancer chemotherapy resistance is a multifactorial phenomenon that can occur at multiple levels (local, regional, and systemic) 125 .…”

Section: Resistancementioning

confidence: 99%

Tumor metabolism, cancer cell transporters, and microenvironmental resistance

Alfarouk

2016

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

Cancer cells reprogram their metabolic machineries to enter into permanent glycolytic pathways. The full reason for such reprogramming takes place is unclear. However, this metabolic switch is not made in vain for the lactate that is generated and exported outside cells is reused by other cells. This results in the generation of a pH gradient between the low extracellular pH that is acidic (pHe) and the higher cytosolic alkaline or near neutral pH (pHi) environments that are tightly regulated by the overexpression of several pumps and ion channels (e.g. NHE-1, MCT-1, V-ATPase, CA9, and CA12). The generation of this unique pH gradient serves as a determining factor in defining ''tumor fitness''. Tumor fitness is the capacity of the tumor to invade and metastasize due to its ability to reduce the efficiency of the immune system and confer resistance to chemotherapy. In this article, we highlight the importance of tumor microenvironment in mediating the failure of chemotherapeutic agents.

show abstract

“…[15][16][17][18][19][20][21] MDR1 expression is the best characterized of these mechanisms. The magnitude of resistance depends on the expression of MDR1 up-regulated by chemotherapy, and the idea of finding modulators that inhibit the function of MDR1 and thereby reverse multidrug resistance has grown in parallel with biochemical and clinical investigations of the molecular mechanism and regulation of MDR1.…”

Section: Mdr1 In Pharmacokinetics and Pharma-codynamicsmentioning

confidence: 99%

MDR1 Genotype-Related Pharmacokinetics and Pharmacodynamics.

Sakaeda

Nakamura

Okumura

2002

Biological & Pharmaceutical Bulletin

169

111

View full text Add to dashboard Cite

The multidrug resistant transporter MDR1/P-glycoprotein, the gene product of MDR1, is a glycosylated membrane protein of 170 kDa, belonging to the ATP-binding cassette superfamily of membrane transporters. MDR1 acts as an energy-dependent efflux pump that exports its substrates out of cells. MDR1 was originally isolated from resistant tumor cells as part of the mechanism of multidrug resistance, but over the last decade, it has been elucidated that human MDR1 is also expressed throughout the body to confer intrinsic resistance to the tissues by exporting unnecessary or toxic exogeneous substances or metabolites. A number of structurally unrelated drugs are substrates for MDR1, and MDR1 and other transporters are recognized as an important class of proteins for regulating pharmacokinetics and pharmacodynamics. In 2000, Hoffmeyer et al. performed a systemic screening for MDR1 polymorphisms and detected 15 single nucleotide polymorphisms (SNPs). They also indicated that a polymorphism in exon 26 at position 3435 (C3435T), a silent mutation, affected the expression level of MDR1 protein in duodenum, and thereby the intestinal absorption of digoxin. To date, the genotype frequencies of C3435T have been investigated extensively using a larger population and interethnic difference has been elucidated, and a total of 28 SNPs have been found at 27 positions on the MDR1 gene. Clinical studies on MDR1 genotype-related MDR1 expression and pharmacokinetics have also been performed around the world; however, results were not always consistent with Hoffmeyer's report. In this review, published reports are summarized for the future individualization of pharmacotherapy based on MDR1 genotyping. In addition, recent investigations have raised the possibility that MDR1 and related transporters play a fundamental role in regulating apoptosis and immunology, and in fact, there are reports of MDR1-related susceptibility to inflammatory bowel disease, HIV infection and renal cell carcinoma. Herein, these issues are also summarized, and the current status of the knowledge in the area of pharmacogenomics of other transporters is briefly introduced.

show abstract

Cancer multidrug resistance

Cited by 292 publications

References 14 publications

In-depth research of multidrug resistance related cell surface glycoproteome in gastric cancer

In-depth research of multidrug resistance related cell surface glycoproteome in gastric cancer

Tumor metabolism, cancer cell transporters, and microenvironmental resistance

MDR1 Genotype-Related Pharmacokinetics and Pharmacodynamics.

Contact Info

Product

Resources

About