IoB Seminar Series: Dr Ping Pui Wong, Improved treatment strategy for advanced breast cancer
Date: 22 February 2017 Time: 15:00 - 16:00
My research focuses on understanding the molecular basis of chemoresistance in cancer treatment.
Although the anti-oestrogen tamoxifen treatment has improved survival for oestrogen receptor positive (ER+) breast cancer patients, eventual resistance is a common and devastating result for over 30% of patients, showing we must improve therapeutic strategies.
Our preliminary studies suggest strongly that expression of MAGEA2 (Melanoma-Associated Antigen 2), and related members of this cancer-testis antigen family, is up-regulated in tamoxifen-resistant tumour cells. Expression of MAGEA2 in tumour lines grown in vitro or as xenografts led to continued proliferation in the presence of tamoxifen.
At the molecular level, we found that MAGEA2 protein localises to the nucleus and forms complexes with p53 and ER?, resulting in repression of the p53 pathway but increased ER-dependent signaling. In a series of ER+, tamoxifen-treated breast cancer patients, we show a highly significant association between MAGEA expression and reduced overall survival, confirming the clinical significance of our observation.
These findings will be used to inform further translational/pre-clinical studies to target MAGEA, or the pathways activated, in conjunction with tamoxifen treatment to improve patient outcomes and establish the utility of MAGEA expression as a marker of de novo or acquired tamoxifen resistance in breast cancer.
|Location:||PP1 Lecture Theatre, People’s Palace, Mile End|
|Contact:||Dr Ping Pui Wong|