The relationship between epidermal growth factor receptor and hedgehog signaling

描述（由申请人提供）：据估计，2010年，美国将有超过140，000人被诊断患有结肠癌和直肠癌，并且将有大约51，000人死于这种疾病。大多数结肠癌相关死亡可归因于转移。因此，更好地了解转移过程可能会导致预后和治疗的进步。 已知表皮生长因子受体（EGF-R）和Hedgehog（Hh）信号传导途径独立地促进许多癌症的发展或进展，包括皮肤、脑、肺、乳腺、前列腺、胰腺、卵巢和结肠的恶性肿瘤。几项研究现在支持这样的观点，即Hh和EGF-R之间的双向串扰可以显著改变单独的任一途径的细胞效应。然而，这些复杂的相互作用在癌症的发展、进展、预后和治疗方面的意义在很大程度上仍未被探索。 本研究计划的目标是确定EGF-R和Hh信号相互作用对人类结肠癌细胞的进展和转移的贡献。具体目的是1）确定EGF-R对Hh介导的结肠癌细胞信号传导、生长和存活的影响，以及2）确定EGF-R和Hh信号传导如何调节小鼠中原位生长的人结肠癌细胞的生长、存活和自发转移。 K 01奖将支持Rebhun博士的职业发展，并将进一步为他在比较和转化癌症研究方面的独立研究生涯做好准备。Rebhun博士是一名委员会认证的临床兽医肿瘤学家（DVM，ACVIM-Oncology文凭），是一名经过双重培训的临床医生/科学家，拥有博士学位。癌症生物学学位。要求提供五年的辅导支持。

DESCRIPTION (provided by applicant): 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.