Nucleic Acid Aptamer Selection Against Her2/neu: An Innovative Method of Inhibiting Her2 to Improve Cancer Treatment

Katharine Heffner kh24992

Human epidermal growth factor receptor 2 (her2/neu) is a transmembrane tyrosine kinase found on many types of cancerous cells(Zhang et. al, 2011). The over expression of her2 on cells is caused by a gene amplification, the cause of which scientist have yet to discover (Lauterlein et. al, 2011). While an over expression of her2 may be found in many cancers, the presence of her2 in breast cancer cells is strongly correlated with chemotherapy resistance and poor recovery statistics (Zhang et. al). Present in approximately 30% of all breast cancers, her2 typically requires a specifically targeted treatment in order for chemotherapy to be effective (Kuo et. al, 2011).

An aptamer is a single strand of nucleic acids that is designed to bind to a target, usually a protein such as her2. The creation of an aptamer designed to bind exclusively to her2 has the potential to become an immensely useful therapeutic. An aptamer for her2 may aid in the effectiveness of already existing cancer treatments such as chemotherapy and slow the growth of cancerous masses. Some drugs like Herceptin, an antibody against her2, are already accredited methods of treating a her2 positive tumor (Kuo et. al, 2011). However, development of an aptamer could potentially create a treatment without some of the complicating side effects of Herceptin, thus making an aptamer against her2 a valuable tool.

Specific Aim 1: Development of an RNA aptamer against her2/neu

Human epidermal growth factor receptor 2 is associated with increased growth, metastasis, and resistance against chemotherapy (Dua et. al). The production of an aptamer that could effectively inhibit the activity of her2 could serve as a useful medication. By making chemotherapy more effective and slowing the growth of cancer cells, an aptamer against her2 could immensely improving the prognosis for many cancer patients (Kuo et. al, 2011).

Her2 may be purchased online from GenWay Biotech, Inc. One mg of her2/neu costs $170 and the catalog number is 06-271-83273.

References

Dua, R. Zhang, R., Nhonthachit, P., Penuel, E., Petropoulos, C. & Parry, G. (2010). EGFR over-expression and activation in high HER2, ER negative breast cancer cell line induces trastuzumab resistance. Breast Cancer Research and Treatment. 122(3), 685-697.

Kuo, H. , Chuang, T., Yeh, M., Hsu, S., Way, T., Chen, P., Wang, S., Chang, Y., Kao, M., Liu, J. (2011). Growth Suppression of HER2-Overexpressing Breast Cancer Cells by Berberine via Modulation of the HER2/PI3K/Akt Signaling Pathway. Journal of Agricultural and Food Chemistry, 59 (15), 8216-8224.

Lauterlein, J. L., Petersen, E. B., Olsen, D. a., Østergaard, B., & Brandslund, I. (2011). Quantification of HER2 autoantibodies in the amplification phenomenon of HER2 in breast cancer. Clinical Chemistry & Laboratory Medicine, 49(5), 877-883. doi:10.1515/CCLM.2011.135.

Zhang, W., Ding, W., Chen, Y., Feng, M., Ouyang, Y., Yu, Y.,& He, Z (2010). Up-regulation of breast cancer resistance protein plays a role in HER2-mediated chemoresistance through PI3K/Akt and nuclear factor-kappa B signaling pathways in MCF7 breast cancer cells Acta Biochim Biophys Sin. 43(8): 647-653.

Link to proposal: https://webspace.utexas.edu/kh24992/Heffner - Nucleic Acid Selection Against Her 2.docx

Link to 1st progress report

Link to final manuscript