Michael P DiGiovanna MD, PhD

Associate Professor of Medicine (Medical Oncology) and of Pharmacology

Research Interests

Breast cancer; HER-2/neu/ErbB-2; IGF1 receptor; EGF receptor; Growth factor receptor tyrosine protein kinases in malignancy; Estrogen receptor; Signal transduction; Breast cancer clinical trials

Current Projects

Therapeutic implications of interactions of IGF-I receptor with HER2 and estrogen receptor

Research Summary

We study signal transduction by growth factor receptor tyrosine kinases, focusing on the EGFR/HER2/ErbB family, including the impact of signaling by these receptors on clinical outcomes and response to targeted therapies for cancer, and their potential as therapeutic targets in novel combination therapies. A major focus in our laboratory has been the interaction of HER2 signaling with estrogen receptor (ER) signaling in breast cancer, and more recently with IGF-I receptor signaling, and the effects of inhibitors of these receptors in combination targeted therapies. We have also found that in breast cancer patients, tumors harboring activated HER2 have adverse prognosis, and these tumors have co-overexpression of EGFR. We continue to study how signaling by these receptors impacts responses to different types of therapies and explore targeting these receptors in combination with other novel targeted therapeutics.

Extensive Research Description

We study signal transduction by growth factor receptor tyrosine kinases, focusing on the EGFR/HER2/ErbB family, including the impact of signaling by these receptors on clinical outcomes and response to targeted therapies for cancer, and their potential as therapeutic targets in novel combination therapies. A major focus in our laboratory has been the interaction of HER2 signaling with estrogen receptor (ER) signaling in breast cancer, and more recently with IGF-I receptor signaling, and the effects of inhibitors of these receptors in combination targeted therapies. We have also found that in breast cancer patients, tumors harboring activated HER2 have adverse prognosis, and these tumors have co-overexpression of EGFR. We continue to study how signaling by these receptors impacts responses to different types of therapies and explore targeting these receptors in combination with other novel targeted therapeutics.


Selected Publications

  • Koay, D.C, Zerillo, C., Narayan, M., Harris, L.N. and DiGiovanna, M.P., “Anti-tumor effects of retinoids combined with trastuzumab or tamoxifen in breast cancer cells: induction of apoptosis by retinoid/trastuzumab combinations”, Breast Cancer Research, 12:R62 [Epub ahead of print], 2010
  • Chakraborty, A.K., Welsh, A., and DiGiovanna, M.P., “Co-Targeting IGF1R enhances growth-inhibitory and pro-apoptotic effects of antiestrogens in human breast cancer cell lines”, Breast Cancer Research and Treatment, DOI: 10.1007/s10549-009-0382-5 (2009), 120:327, 2010
  • Chakraborty, A.K. Liang, K. and DiGiovanna, M.P., “Co-Targeting insulin-like growth factor I receptor and HER2: Dramatic effects of HER2 inhibitors on nonoverexpressing breast cancer”, Cancer Research, 68:1538-1545, 2008
  • DiGiovanna, M.P., Stern, D.F., Edgerton, S., Broadwater, G., Dressler, L., Budman, D.R., Henderson, I.C., Norton, L., Liu, E.T., Muss, H.B., Berry, D., Hayes, D.F. and Thor, A.D., for the Cancer and Leukemia Group B, “Correlation of activation of ErbB2 (HER-2/neu) with benefit of dose-escalation of doxorubicin/cyclophosphamide in the adjuvant treatment of breast cancer”, Journal of Clinical Oncology, 26:2364-2372, 2008
  • DiGiovanna, M.P., Stern, D.F., Edgerton, S., Whalen, S.G., Moore, D. and Thor, A.D. (2005). ErbB-2 activation, epidermal growth factor receptor expression and prognosis in breast cancer patients. J. Clin. Oncology 23:1152-1160.
  • Wang, C.-X., Koay, D.C., Edwards, A., Lu, Z., Mor, G., Ocal, I.T., and DiGiovanna, M.P., “In vitro and in vivo effects of combination of trastuzumab (Herceptin) and tamoxifen in breast cancer”, Breast Cancer Research and Treatment, 92:251-263, 2005
  • Argiris, A., Wang, C.-X., Whalen, S.G., and DiGiovanna, M.P. (2004). Synergistic interactions between tamoxifen and Trastuzumab (Herceptin). Clinical Cancer Res. 10:1409-1420.

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