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.
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.
Cumulative risk analysis revealed 3 unfavorable variants that increased significantly the risk of developing ovarian cancer (p.Ile1145 = ABCB1+ p.Asp1853Asn ATM+ p.Ser406Ala ATP7B- OR 7,47; p = 0,002) and significantly modified the progression free survival (PFS) of the patients, and also two favorable genotypes which protected against ovarian cancer (p.Arg952Lys ATP7B+ p.Arg72Pro TP53- OR 0,50; p = 0,008).
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.
CYP2C8*3 and three ABCB1 polymorphisms were chosen for primary analysis, and a host of other candidate genes was explored in 92 prospectively recruited Scandinavian Caucasian women with primary ovarian cancer who were treated with paclitaxel and carboplatin.
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 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.
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 inhibition of P-glycoprotein (P-gp) was determined in vitro, and the respective sensitization of doxorubicin-resistant ovarian carcinoma overproducing P-gp was detected.
P-glycoprotein was positive on luminal surfaces of lining cells of ovarian cancer and on those of inclusion cysts from which epithelial ovarian cancer is considered to develop.
TUBB3, ERCC1 and P-gp are involved in the occurrence and development of ovarian cancer and can be used as important indexes judging the severity of ovarian cancer, providing a reference for the occurrence and development of the disease in ovarian cancer patients in clinical practice.
The demonstration of elevated P-glycoprotein in ovarian carcinomas indicates that P-glycoprotein overexpression is not limited to experimental tumor models.
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.