Breast cancer is one of the most significant causes ofcancer death. It’s a disease in which cells in the breast become abnormal andmultiply uncontrollably to form a tumor. It is considered as one the mostcommon cancer in women worldwide and accounts for 25.1% of all cancers(Ghoncheh et al., 2016). The tumor suppressor genes for breast cancer calledBRCA1 and BRCA2 genes, which stands for BReast CAncer, werediscovered in the 1990s. Dr. Mary-Claire King and her group began the researchin 1979 to determine why some families were severely affected by breast cancer.
They found that women whose sisters or mothers are affected by the disease havea higher lifetime risk to develop breast cancer. Then they located the regionon chromosome 17q21 in families with early-onset breast cancer for whichlikelihood of co-inheritance with breast cancer (Hurst, 2014). In 1990, theexistence of breast cancer genes, which named by Dr. King BRCA1, was proven bymapping predispositions to young-onset breast cancer to that chromosome infamilies (King, 2014). Mark Skolnick at Myriad Genetics in 1994 sequencedBRCA1, and a year after that Michael Stratton and Richard Wooster mapped BRCA2in (1995). The DNA is the genetic blueprint which needs to be kept intact, andas every cell is sustaining DNA lesions, this damage needs to be repaired. Thetumor suppressor BRCA1 and BRCA2 proteins are required formaintaining chromosomal stability.
These proteins play an essential rolein DNA repair, ? homologousrecombination, cell cycle, transcriptional regulation, and protein degradation.The BRCA germline mutation in either gene leads abnormalities and tumorigenesis(Hurst, 2014). Approximately 85% of women who carry BRCA1 and BRCA2 mutationwill have the risk of developing breast cancer before age 70? (Tutt and Ashworth, 2002). Thecomprehension of cells mechanism in responding and repairing DNA damage isessential in treatments development. Based on cell repair mechanism, syntheticlethality concept provides anticancer therapies such as Poly (ADP-ribose)polymerase (PARP) inhibitors.
A decade after discovering BRCA genes, PARPinhibitors have been proven to be a beneficial treatment for patients withgermline BRCA1/2 mutations (Walsh, 2015).