Title:BRCA1-Associated Triple-Negative Breast Cancer and Potential Treatment for Ruthenium-Based Compounds
Volume: 16
Issue: 7
Author(s): Khwanjira Hongthong and Adisorn Ratanaphan
Affiliation:
关键词:
BRCA1；三阴性乳腺癌（TNBC）；钌配合物。
摘要: 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.
