Edward J. Gunther, M.D.
Penn State Hershey Cancer Institute
500 University Drive
Hershey, PA 17033
Tel: 800-243-1455 / 717-531-6585 Fax: 717-531-0429
Patient Services Provided
Clinical Research - Breast Cancer
Fellowship, Hematology/Oncology, Hospital of the University of Pennsylvania (1999) Residency, Internal Medicine, Hospital of the University of Pennsylvania (1995) M.D., Yale University School of Medicine (Connecticut) (1993)
My colleagues and I employ genetically modified mice to uncover molecular and cell biological mechanisms underlying tumor escape. Toward this end, we use novel mouse models that permit reversible activation of oncogenic signaling pathways within mammary epithelium, the tissue compartment in which breast cancers arise. The resulting mice are programmed to develop mammary tumors that faithfully recapitulate key features of human breast cancer, including local invasion at the primary tumor site and metastatic spread to distant organs. Importantly, these mouse models permit oncogenic signaling to be shut off in established tumors, thereby simulating the action of an idealized targeted therapeutic.
We find that, although established mammary cancers regress following abrogation of oncogenic signaling, they invariably leave behind subclinical disease with latent malignant potential. By developing methods for propagating latent malignancy in vivo, we have begun to define biological properties of dormant mammary cancer, an essential and largely unexplored link to breast cancer relapse. Ultimately, by mapping routes to tumor escape and uncovering mechanisms that enable tumor dormancy, we hope to design improved treatment strategies that prevent breast cancer relapse in patients.
Debies MT, Gestl SA, Mathers JL, Mikse OR, Leonard TL, Moody SE, Chodosh LA, Cardiff RD, Gunther EJ
Tumor escape in a Wnt1-dependent mouse breast cancer model is enabled by p19/p53 pathway lesions but not p16 loss.
Journal of Clinical Investigation, 118 (1):51-63. 2008. Gestl SA, Leonard TL, Biddle JL, Debies MT, Gunther EJ
Dormant Wnt-initiated mammary cancer can participate in reconstituting functional mammary glands.
Journal of Molecular Cell Biology, 27:195-207, 2007. Gunther EJ, Moody SE, Belka GK, Hahn KT, Innocent N, Dugan KD, Cardiff RD, Chodosh LA
Impact of p53 loss on reversal and recurrence of conditional Wnt-induced tumorigenesis.
Genes and Development, 17:488-501, 2003 Gunther EJ, Belka GK, Wertheim GB, Wang J, Hartman JL, Boxer RB, Chodosh LA
A novel doxycycline-inducible system for the transgenic analysis of mammary gland biology.
The FASEB Journal (Federation of American Societies for Experimental Biology), 16:283-292, 2002 D'Cruz CM, Gunther EJ, Boxer RB, Hartman JL, Sintasath L, Moody SE, Cox JD, Ha SI, Belka GK, Golant A, et al.
c-MYC induces mammary tumorigenesis by means of a preferred pathway involving spontaneous Kras2 mutations.
Nature Medicine, 7:235-239, 2001