We attempted to gain insight into the potential contribution of ovarian cancer genomic instability resulted from TP53 mutation to the aberrant expression of multidrug resistance gene MDR1.
The finding that the compound induced significantly more cell death in Pgp/MDR1 overexpressing OC cells compared to vincristine and paclitaxel warrants further development of the compound as a new therapy for OC patients with treatment refractory tumors and/or relapsing disease.
The goal of this study is to evaluate the ability of HA-PEI/HA-PEG to deliver MDR1 siRNA and the efficacy of the combination of HA-PEI/HA-PEG/MDR1 siRNA with paclitaxel to suppress growth of ovarian cancer.
These preclinical data suggest that a fiber-modified adenovirus vector under the control of the MDR1 promoter represents a promising treatment strategy for platinum-pretreated ovarian cancer as a single agent or in combination with conventional anticancer drugs.
Our data point at IMP-1 and MDR1 as indicators for response to therapy, and at IMP-1 as a novel therapeutic target for overcoming multidrug resistance of ovarian cancer.
The mdr-1 polymorphism G2677T/A in exon 21 correlates with the paclitaxel response in ovarian cancer and may be important for the function of P-glycoprotein and resistance to paclitaxel and provide useful information for individualized therapy.
The drug concentrations applied referred to clinical relevant doses. mdr1 mRNA expression was significantly higher in specimens from recurrent ovarian cancer incubated in paclitaxel than in specimens from chemotherapy-naive ovarian cancer.
To fill this gap, we investigated the rate of gene amplification of the mdr1-gene in 63 recurrent ovarian carcinomas and we determined the resistance pattern of these cells using an ex vivo assay.
The presence of even very low levels of MDR1 mRNA correlated with the lack of response to MDR regimens in these tumor types (P < .035 for ovarian carcinomas, P < .029 for SCLCs, and P < .0005 for both tumor types; Fisher's Exact Test).
Although drug resistance is a major problem in treatment of ovarian cancer, resistance to the drugs most active against these tumors probably occurs through a mechanism other than expression of the MDR1 gene product.