alexa MUC1* is a determinant of trastuzumab (Herceptin) resistance in breast cancer cells.


Journal of Glycobiology

Author(s): Fessler SP, Wotkowicz MT, Mahanta SK, Bamdad C

Abstract Share this page

Abstract In the United States, 211,000 women are diagnosed each year with breast cancer. Of the 42,000 breast cancer patients who overexpress the HER2 growth factor receptor, <35\% are responsive to treatment with the HER2-disabling antibody, called trastuzumab (Herceptin). Despite those statistics, women diagnosed with breast cancer are now tested to determine how much of this important growth factor receptor is present in their tumor because patients whose treatment includes trastuzumab are three-times more likely to survive for at least 5 years and are two-times more likely to survive without a cancer recurrence. Unfortunately, even among the group whose cancers originally respond to trastuzumab, 25\% of the metastatic breast cancer patients acquire resistance to trastuzumab within the first year of treatment. Follow-on "salvage" therapies have prolonged life for this group but have not been curative. Thus, it is critically important to understand the mechanisms of trastuzumab resistance and develop therapies that reverse or prevent it. Here, we report that molecular analysis of a cancer cell line that was induced to acquire trastuzumab resistance showed a dramatic increase in the amount of the cleaved form of the MUC1 protein, called MUC1*. We recently reported that MUC1* functions as a growth factor receptor on cancer cells and on embryonic stem cells. Here, we show that treating trastuzumab-resistant cancer cells with a combination of MUC1* antagonists and trastuzumab, reverses the drug resistance. Further, HER2-positive cancer cells that are intrinsically resistant to trastuzumab became trastuzumab-sensitive when treated with MUC1* antagonists and trastuzumab. Additionally, we found that tumor cells that had acquired Herceptin resistance had also acquired resistance to standard chemotherapy agents like Taxol, Doxorubicin, and Cyclophosphamide. Acquired resistance to these standard chemotherapy drugs was also reversed by combined treatment with the original drug plus a MUC1* inhibitor. This article was published in Breast Cancer Res Treat and referenced in Journal of Glycobiology

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

  • International Conference on Glycobiology
    Sep 21-22, 2017, Crowne Plaza Houston River Oaks, Houston, USA
  • 2nd International Conference on Biochemistry
    Sep 21-22, 2017 Macau, Hong Kong
  • International Conference on Glycobiology
    Oct 02-04, 2017 Atlanta, USA
  • 4th International Conference on Glycobiology and Glycochemistry
    July 16-18, 2018 Melbourne, Australia
  • 4th Glycobiology World Congress
    September 17-19, 2018 Rome, Italy
Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version