PARP inhibitors in Treatment Breast and Ovarian cancer

Discovering the concept of synthetic lethality has provided new background for the development of targeted therapies. Synthetic lethality is a condition which two genetic aberration create positive result in therapies. In cancer cells with BRCA1 and BRCA2 loss of function that have deficiency in DNA repair pathway by homologous recombination, inhibition of PARP1 enzymatic activity leads to converted single strand breaks to double strand breaks but cannot be repaired by homologous recombination. Inhibition of PARP by PARP inhibitors shows new targeted therapy for cancers with BRCA1/2 mutations. However loss of function of various proteins that have role in double strand break repair other than BRCA1 and BRCA2 has been suggested to be synthetically lethal with PARP inhibition. Inactivation of these genes reported in many human cancers, the most important genes in breast and ovarian cancers was BRCA1/2. Loss of function of these genes are biomarker for using PARP inhibitors to treatment. In this review we discuss about the effect of PARP inhibitors in treatment process of breast and ovarian cancer and prostate cancer that harbor BRCA1 and BRCA2 genetic deficiency.