In breast cancer, 25 percent of recurrences may occur within 10 years after initial therapies. It has been hypothesized that breast cancer stem cells (CSCs) may be responsible for the recurrence since they are more resistant to radiation and chemotherapy. However, the mechanisms underlying this resistance have remained unclear. It had been demonstrated that the glioma stem cells promote radioresistance by preferential activated DNA damage checkpoint response, contributing more effective DNA damage repair.
Similarly, by detecting DNA damage markers 53BP1 and γ-H2AX, our laboratory has also shown that CSCs from p53-null mammary gland tumors and primary human breast cancer xenografts, Lin-CD29HCD24H and ALDH+, respectively, have more efficient DNA damage repair as compared to the majority of tumor cells. Additional studies, however, have to be undertaken to demonstrate the efficiency of the DNA damage response (DDR) in breast CSCs indeed correlate with the radioresistance.
There are two distinct mechanisms to repair DNA double strain breaks—homologous recombination (HR) and non-homologous end joining (NHEJ). Recent studies have demonstrated that adult stem cells, including hair follicle bulge stem cells and quiescent hematopoietic stem cells, have higher NHEJ activity in response to ionizing irradiation (IR), contributing to a faster but error-prone DNA repair. In my study, I will also investigate how breast CSCs functionally respond to and repair DNA damage. More importantly, I will selectively target some known regulators of DDR in CSCs in order to sensitize them to conventional therapies for future clinical application.
- Joined Lab: May 2010
- Position: Graduate Student - CMB Program
- Degrees: National Chung Hsing University, Taiwan, 2006
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