It is estimated that over 140,000 people in the United States will be diagnosed with cancer of the colon and rectum and approximately 51,000 deaths will occur from this disease in 2010. The majority of colon cancer-related deaths can be attributed to metastasis. Therefore, a better understanding of the metastatic process may lead to prognostic and therapeutic advancements. Epidermal growth factor receptor (EGF-R) and Hedgehog (Hh) signaling pathways are independently known to contribute to the development or progression of many cancers including malignancies of the skin, brain, lung, breast, prostate, pancreas, ovary, and colon. Several studies now support the notion that bi- directional cross-talk between Hh and EGF-R can dramatically alter the cellular effects of either pathway alone. However, the implication of these complex interactions in regard to the development, progression, prognosis, and treatment of cancer remain largely unexplored. The goal of this research plan is to determine the contribution of EGF-R and Hh signaling interactions to the progression and metastasis of human colon cancer cells.
The specific aims are to 1) Determine the effects of EGF-R on Hh mediated colon cancer cell signaling, growth, and survival, and to 2) Determine how EGF-R and Hh signaling modulates growth, survival, and spontaneous metastasis of human colon cancer cells growing orthotopically in mice. The K01 award would support Dr. Rebhun's career development and will further prepare him for an independent research career in comparative and translational cancer research. Dr. Rebhun is a board certified clinical veterinary oncologist (DVM, Diplomate ACVIM-Oncology) and is a dual-trained clinician/scientist with a Ph.D. degree in cancer biology. Five years of mentored support is requested.
Colon cancer is the third most common cause of cancer related death in both men and women and it is estimated that over 50,000 people will die of this disease within the United States in 2010. A better understanding of colon cancer cell signaling and metastasis is required in order to advance treatment of this disease. The goal of this project is to understand and describe interactions between specific cell signaling pathways that have individually been implicated in the progression of colon cancer.
|Withers, Sita S; York, Daniel; Johnson, Eric et al. (2018) In vitro and in vivo activity of liposome-encapsulated curcumin for naturally occurring canine cancers. Vet Comp Oncol 16:571-579|
|Rebhun, R B; Kass, P H; Kent, M S et al. (2017) Evaluation of optimal water fluoridation on the incidence and skeletal distribution of naturally arising osteosarcoma in pet dogs. Vet Comp Oncol 15:441-449|
|York, D; Withers, S S; Watson, K D et al. (2017) Enrofloxacin enhances the effects of chemotherapy in canine osteosarcoma cells with mutant and wild-type p53. Vet Comp Oncol 15:1087-1100|
|Skorupski, K A; Uhl, J M; Szivek, A et al. (2016) Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized, phase III trial. Vet Comp Oncol 14:81-7|
|Withers, Sita S; Lawson, Corinne M; Burton, Andrew G et al. (2016) Management of an invasive and metastatic Sertoli cell tumor with associated myelotoxicosis in a dog. Can Vet J 57:299-304|
|Collette, S A; Allstadt, S D; Chon, E M et al. (2016) Treatment of feline intermediate- to high-grade lymphoma with a modified university of Wisconsin-Madison protocol: 119 cases (2004-2012). Vet Comp Oncol 14 Suppl 1:136-46|
|Burton, J H; Stanley, S D; Knych, H K et al. (2016) Frequency and Severity of Neutropenia Associated with Food and Drug Administration Approved and Compounded Formulations of Lomustine in Dogs with Cancer. J Vet Intern Med 30:242-6|
|Lejeune, A; Skorupski, K; Frazier, S et al. (2015) Aggressive local therapy combined with systemic chemotherapy provides long-term control in grade II stage 2 canine mast cell tumour: 21 cases (1999-2012). Vet Comp Oncol 13:267-80|
|Kol, Amir; Arzi, Boaz; Athanasiou, Kyriacos A et al. (2015) Companion animals: Translational scientist's new best friends. Sci Transl Med 7:308ps21|
|Shahi, Mehdi H; Zazpe, Idoya; Afzal, Mohammad et al. (2015) Epigenetic regulation of human hedgehog interacting protein in glioma cell lines and primary tumor samples. Tumour Biol 36:2383-91|
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