title: BRCA1-Associated Triple-Negative Breast Cancer and Potential Treatment for Ruthenium-Based Compounds.
abstract: Triple-negative breast cancer (TNBC) is defined by the absence of expression of estrogen receptor (ER), progesterone receptor (PR), and a lack of overexpression or amplification of human epidermal growth factor receptor 2 (HER2). The clinicopathological characteristics of TNBC include a high grading, a high rate of cell proliferation and a greater degree of chromosomal rearrangement. Patients with triple-negative breast cancer are more likely to be drug resistant and more difficult to treat, and are also frequently BRCA1 mutants. Methylation of the BRCA1 promoter region is associated with a reduction of the BRCA1 mRNA level. TNBC patients with a methylated BRCA1 had a better disease-free survival compared with those with non-methylated BRCA1. From a therapeutic perspective, the expression level of BRCA1 has been a major determinant of the responses to different classes of chemotherapy. BRCA1-dysfunctional tumors are hypersensitive to DNA damaging chemotherapeutic agents like platinum drugs. Although platinum based drugs are currently widely used as conventional chemotherapeutic drugs in breast cancer chemotherapy, their use has several disadvantages. It is therefore of interest to seek out alternative therapeutic metal-based compounds that could overcome the limitations of these platinum based drugs. Ruthenium-based compounds could be the most promising alternative to the platinum drugs. This review highlights the use of BRCA1 as a predictive marker as well as for a potential drug target for anticancer ruthenium compounds.
authors: Khwanjira
authors: K
authors: Hongthong
authors: Laboratory of Pharmaceutical Biotechnology, Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Songkhla 90112, Thailand. adisorn.r@psu.ac.th.
authors: Adisorn
authors: A
authors: Ratanaphan
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000378:metabolism*; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012428:Ruthenium / Q000627:therapeutic use*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D012428:Ruthenium; C492913:BRCA1 protein, human; C508053:ERBB2 protein, human