title: Gene Therapeutic Approaches to Overcome ABCB1-Mediated Drug Resistance.
abstract: Multidrug resistance (MDR) to pharmaceutical active agents is a common clinical problem in patients suffering from cancer. MDR is often mediated by over expression of trans-membrane xenobiotic transport molecules belonging to the superfamily of ATP-binding cassette (ABC)-transporters. This protein family includes the classical MDR-associated transporter ABCB1 (MDR1/P-gp). Inhibition of ABC-transporters by low molecular weight compounds in cancer patients has been extensively investigated in clinical trials, but the results have been disappointing. Thus, in the last decades alternative experimental therapeutic strategies for overcoming MDR were under extensive investigation. These include gene therapeutic approaches applying antisense-, ribozyme-, RNA interference-, and CRISPR/Cas9-based techniques. Various delivery strategies were used to reverse MDR in different tumor models in vitro and in vivo. Results and conclusions of these gene therapeutic studies will be discussed.
authors.affiliation: Fachbereich Pathologie, Vivantes Klinikum Neukölln, Rudower Allee 48, 12351, Berlin, Germany. hermann.lage@vivantes.de.
authors.forename: Hermann
authors.initials: H
authors.lastname: Lage
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D064130:CRISPR-Associated Proteins / Q000235:genetics / Q000378:metabolism; D064113:CRISPR-Cas Systems; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000067492:RNAi Therapeutics; D014162:Transfection
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D064130:CRISPR-Associated Proteins
keywords: CRISPR/Cas9; Cancer; Gene therapy; Multidrug resistance; RNA interference