PARP Inhibition: A Method of Treating and Preventing Certain Cancers

Breast cancer is one of the largest causes of cancer related deaths in women. Less than 5% of breast cancer cases are genetically inherited and most often develop after menopause. The BRCA gene mutation is a genetic inheritance which increases ones chances of developing breast cancer at a young age tenfold. Recent research has proposed a method of treatment in genetically inherited breast cancers by taking advantage of the impaired DNA repair pathway caused by the BRCA mutation. The combination of a BRCA mutation, which leads to deficient double strand DNA repair, and PARP inhibition, which leads to deficient single strand DNA repair, has proven to be synthetically lethal to tumor cells. Clinical trials are determining if this method should be used as a mono-treatment or as an enhancer to other treatment options. Research has also shown that PARP inhibition may be extended to non-genetic cancers as well by targeting similar proteins involved in DNA repair and cell cycle regulation. The most effective inhibitors, their dosages, and side effects are still being studied in clinical trials. The purpose of this paper is to determine the most effective way to take advantage of the synthetically lethal relationship between PARP inhibition and DNA damage repair deficiencies