Colorectal cancer afflicts 135,000 Americans per year and 38% of these patients will die of disseminated disease most commonly to liver lung and bone. Of the patients that die of this disease, 70% have liver metastases and a significant 10% have liver-only disease. Even in those patients with metastases to multiple organ sites, the extent of liver disease remains the primary determinant of survival. Over the last two decades we have empirically learned that patients with liver only metastases have improved survival when treated aggressively. Untreated, patients with hepatic only metastases have a median survival of only 12-21 months and the five year survival of patients with unresected metastasis is close to 0%. In sharp contrast, resection of metastases in patients with liver only disease yields five year survival rates of 20-40% and 10 year survival rates of 20%. Furthermore, the most common site of disease recurrence after resection is the liver. Consequently, liver metastases are a primary determinant of survival in patients with stage IV colorectal cancer. Building upon preliminary data linking ERBB receptor activity to colorectal cancer progression and metastasis, we hypothesize that small molecule ERBB inhibitors, if optimally employed, will retard the growth and dissemination of metastatic colorectal cancer. We also hypothesize that colorectal cancer can also arise independently of ERBB and that an understanding of these mechanisms will allow us to design better therapies. Thus, using a combination of clinical samples and pre-clinical mouse models, we propose to investigate the mechanism of how metastatic colon cancer uses EGFR and other ERBB receptor signaling to establish residency in the liver and to identify markers for response to dual EGFR/ERBB2 inhibitors during treatment of metastatic lesions. Experiments are planned to identify transcriptional profiles unique to EGFR independent colorectal cancer development.

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National Cancer Institute (NCI)
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University of North Carolina Chapel Hill
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Asher, Gary N; Xie, Ying; Moaddel, Ruin et al. (2017) Randomized Pharmacokinetic Crossover Study Comparing 2 Curcumin Preparations in Plasma and Rectal Tissue of Healthy Human Volunteers. J Clin Pharmacol 57:185-193
Gao, Xingming; Zhu, Mengyuan; Fan, Haiying et al. (2015) A fluorescent bisboronic acid compound that selectively labels cells expressing oligosaccharide Lewis X. Bioorg Med Chem Lett 25:2501-4
Keku, Temitope O; Dulal, Santosh; Deveaux, April et al. (2015) The gastrointestinal microbiota and colorectal cancer. Am J Physiol Gastrointest Liver Physiol 308:G351-63
Lin, Ja-An; Zhu, Hongtu; Mihye, Ahn et al. (2014) Functional-mixed effects models for candidate genetic mapping in imaging genetic studies. Genet Epidemiol 38:680-91
Nugent, Julia L; McCoy, Amber N; Addamo, Cassandra J et al. (2014) Altered tissue metabolites correlate with microbial dysbiosis in colorectal adenomas. J Proteome Res 13:1921-9
Zhu, Hongtu; Ibrahim, Joseph G; Tang, Niansheng (2014) Bayesian Sensitivity Analysis of Statistical Models with Missing Data. Stat Sin 24:871-896
Nikolaishvilli-Feinberg, Nana; Cohen, Stephanie M; Midkiff, Bentley et al. (2014) Development of DNA damage response signaling biomarkers using automated, quantitative image analysis. J Histochem Cytochem 62:185-96
Wang, Hansong; Burnett, Terrilea; Kono, Suminori et al. (2014) Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A. Nat Commun 5:4613
McCoy, Amber N; Araújo-Pérez, Félix; Azcárate-Peril, Andrea et al. (2013) Fusobacterium is associated with colorectal adenomas. PLoS One 8:e53653
Kang, Melissa; Edmundson, Patrick; Araujo-Perez, Felix et al. (2013) Association of plasma endotoxin, inflammatory cytokines and risk of colorectal adenomas. BMC Cancer 13:91

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