Expression of multidrug resistance-1 protein inversely correlates with paclitaxel response and survival in ovarian cancer patients: a study in serial samples

Coexpression of invasive markers (uPA, CD44) and multiple drug-resistance proteins (MDR1, MRP2) is correlated with epithelial ovarian cancer progression

“…Xing et al (2007) recently reported that knock down of P-glycoprotein reverses taxol resistance in ovarian cancer multicellular spheroids. An increased expression of MDR1 was found to be associated with an unfavourable prognosis of ovarian cancer in some studies (Materna et al, 2004;Penson et al, 2004), but not in others (Yokoyama et al, 1999;Ozalp et al, 2002). These inconsistent results suggest that it is necessary to further investigate the correlation of MDR1 expression with ovarian cancer prognosis using a relatively large number of ovarian cancer tissues before chemotherapy.…”

“…Drugresistance proteins such as MDR1 and MRP2 are the best-known mediators of resistance to anticancer drugs, extruding many types of drugs from cancer cells, thereby conferring resistance to those agents. Although previous reports have shown that the presence of uPA, CD44 and MDR proteins was related to EOC progression and prognosis (Kayastha et al, 1999;Konecny et al, 2001;Penson et al, 2004), their expression and link between these two markers in primary EOCs and in metastatic microenvironment have not been fully investigated.…”

Treatment-Related Protein Biomarker Expression Differs between Primary and Recurrent Ovarian Carcinomas

“…These observations are particularly relevant because these biomarkers are associated with resistance to chemotherapies [i.e., PGP for taxanes and anthracyclines (10) and ERCC1 for platinum (16)] used in the treatment of ovarian cancer. Previous investigators have also reported increased expression of PGP in recurrent ovarian cancers (9,10), although other studies did not show elevated levels in recurrent tumors (12,17,18). The reasons for these disparate results may be due to differences in the patient disease characteristics, sample size, assay type, and conditions (e.g., mRNA vs. protein, antibody, and methodology), cut points defined for high PGP expression, or type of prior chemotherapy.…”

“…Among these are the reports of elevated P-glycoprotein (PGP) levels in some recurrent ovarian tumors (9)(10)(11). However, direct comparisons of the expression of these markers in ovarian tumors present at relapse following chemotherapy treatment and in the primary tumor from the same patient are rare and have typically measured fewer than 3 proteins [i.e., PGP (12), MT (13), or TOPO1, HER2, and Ki67 (14)]. Results from such matched pair analyses of a panel of clinically relevant biomarkers would show whether primary specimens provide the same information as recurrent specimens, or whether biopsies should be taken at recurrence for molecular profiling analysis to inform selection of salvage therapies.…”

Are ABCB1 (P-glycoprotein) polymorphisms clinically relevant in ovarian cancer? – Finally an Answer!

“…Although it seems likely that cancer cells use several different types of ABC transporters to gain drug resistance most clinical studies have focused on P-glycoprotein. Increased expression of P-glycoprotein in tumor tissues has been associated with adverse clinical outcome in ovarian cancer [3][4][5][6][7]. However, many of these studies were small and most used varying methods to assess P-glycoprotein levels, thus uniform conclusions on the clinical relevance of Pglycoprotein expression for drug response in ovarian cancer cannot yet be made.…”