A Systematic Review of Genes Involved in the Inverse Resistance Relationship Between Cisplatin and Paclitaxel Chemotherapy: Role of BRCA1

Abstract

A systematic review of cell models of acquired drug resistance not involving genetic manipulation showed that 80% of cell models had an inverse resistance relationship between cisplatin and paclitaxel [1] . Here we systematically review genetically modified cell lines in which the inverse cisplatin/paclitaxel resistance phenotype has resulted. This will form a short list of genes which may play a role in the mechanism of the inverse resistance relationship as well as potential markers for monitoring the development of resistance in the clinical treatment of cancer. The literature search revealed 91 genetically modified cell lines which report toxicity or viability/apoptosis data for cisplatin and paclitaxel relative to their parental cell lines. This resulted in 26 genes being associated with the inverse cisplatin/paclitaxel phenotype. The gene with the highest number of genetically modified cell lines associated with the inverse resistance relationship was BRCA1 and this gene is discussed in detail with reference to chemotherapy response in cell lines and in the clinical treatment of breast, ovarian and lung cancer. Other genes associated with the inverse resistance phenotype included dihydrodiol dehydrogenase (DDH) and P-glycoprotein. Genes which caused cross resistance or cross sensitivity between cisplatin and paclitaxel were also examined, the majority of these genes were apoptosis associated genes which may be useful for predicting cross resistance. We propose that BRCA1 should be the first of a panel of cellular markers to predict the inverse cisplatin/paclitaxel resistance phenotype.3

Carboplatin and taxol resistance develops more rapidly in functional BRCA1 compared to dysfunctional BRCA1 ovarian cancer cells

“…This is usually greater than the increase in resistance seen per round from single-agent taxol treatments. This is the opposite of what we would have predicted given the inverse resistance relationship between platinum and taxanes (Stordal et al 2009). We hypothesised that pre-treatment with one agent would sensitise to the other.…”

“…A subsequent systematic review by (Stordal et al 2009), revealed that BRCA1 was the mostly likely genetic player in this relationship. Cells with BRCA1 defects have reduced efficiency in repairing DNA adducts and show increased apoptosis in response to platinums conferring sensitivity (Foulkes 2006;Xing et al 2006).…”

Correlation between BRCA1 expression and clinicopathological factors including brain metastases in patients with non-small-cell lung cancer

“…It is also known that increased BRCA1 protein expression in prostate cancer is associated with significantly higher Gleason score, and more advanced stage 6 , as well as a poor outcome in thymic epithelial tumors 9 . A wealth of data from cell lines, mouse models and more recently from clinical studies have shown that BRCA1 can modulate response to chemotherapy [10][11][12][13] . BRCA1 mutations are not found in lung cancer, but decreased BRCA1 mRNA and protein expression due to promoter hypermethylation were found in 30% of NSCLC patients mostly in adenocarcinoma subtypes (P<0.014) (ref.…”

Predictive value of BRCA1 expression on the efficacy of chemotherapy based on anti-microtubule agents: a pooled analysis across different malignancies and agents

“…Because of this, the mechanism of resistance to anti-microtubule agents earn widespread concerns and many studies have reported on the subject. Several mechanisms explain the resistance, including decrease of the cellular accumulation mediated by P-glycoprotein (26) exportation and altered expression or post-translational modification of tubulin or other microtubule regulatory proteins (27). Recently, some studies have reported on the relationship a n d m e c h a n i s m b e t w e e n B R C A 1 e x p r e s s i o n a n d chemotherapy outcomes for carcinoma, but the results were controversial.…”