Author(s): Khawla Al-Kuraya
Patients with aggressive breast cancer (BC) subtypes usually do not have favorable prognosis despite the improvement in treatment modalities. These cancers remain a major cause of morbidity and mortality in females. This has fostered a major effort to discover actionable molecular targets to treat these patients. Poly ADP ribose polymerase (PARP) is one of these molecular targets that are under comprehensive investigation for treatment of such tumors. However, its role in the pathogenesis of BC from Middle Eastern ethnicity has not yet explored. Therefore, the authors examined the expression of PARP protein in a large cohort of over 1000 Middle Eastern BC cases using immunohistochemistry. Correlation with clinico-pathological parameters was performed.
Nuclear PARP overexpression was observed in 44.7% of all BC cases and was significantly associated with aggressive clinico-pathological markers. Interestingly nuclear PARP overexpression was an independent predictor of poor prognosis. PARP overexpression was also directly associated with XIAP overexpression, with PARP and XIAP co-expression in 15.8% (159/1008) of our cases. It was observed that the combined inhibition of PARP by olaparib and XIAP by embelin significantly and synergistically inhibited cell growth and induced apoptosis in BC cell lines
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