Abstract
Multidrug resistance (MDR) phenotype emerging from chemotherapy is a major problem in managing patients with metastatic cancers. The discovery that a cardiovascular drug, verapamil, can bind to P-glycoprotein and reverse MDR initiated serious research efforts in MDR-reversal by various compounds and modes of pharmacological modifiers. Those include major calcium channel blockers such as bepridil, diltiazem, felodipine, isradipine, nicardipine, nifedipine and nimodipine, verapamil and analogs; calmodulin antagonists; antibiotics and analogs; indole alkaloids; cyclosporins and analogs; hormones and antihormones; pharmaceutical emulsifying surfactants; liposomal encapsulation; etc. The majority of the studies targeted one of the MDR mechanisms, P-glycoprotein. These studies have been successful under in vitro and limited in vivo animal conditions; the correlations for clinical trails are still lacking. Therefore, an effective MDR-reversing chemotherapy is not available. It is the purpose of this chapter to review the past and current experimental reversal of MDR and, in particular, the importance in targeting drug resistance in relevant cancer metastasis models.
Original language | English (US) |
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Title of host publication | Drug Resistance in Cancer Cells |
Publisher | Springer US |
Pages | 21-52 |
Number of pages | 32 |
ISBN (Print) | 9780387894447 |
DOIs | |
State | Published - 2009 |
Keywords
- Animal models
- Apoptosis
- MDR
- Metastasis
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- General Biochemistry, Genetics and Molecular Biology