Candidate: Andrew C. Chang, MD, is a junior faculty member in the Department of Surgery, Section of Thoracic Surgery whose career goal is to perform translational research focusing on the tumorigenesis of esophageal cancer, and specifically to identify and evaluate genes associated with tumor chemoresistance. Research Plan: The incidence of esophageal adenocarcinoma is burgeoning. Despite advances in multimodality treatment, esophageal cancer remains highly lethal in the United States, with overall five-year survival of only 15%. Current regimens of both preoperative (neoadjuvant) and postoperative (adjuvant) chemotherapy and radiation have had only a slight impact on long-term survival following operation. The candidate hypothesizes that the identification of genes associated with tumor chemoresistance will lead to validation of novel markers for treatment response that can be assessed from diagnostic pretreatment biopsies. Development of such biomarkers would permit patient-directed and targeted therapy of esophageal cancer, potentially limiting treatment-related toxicity. Candidate genes and their associated proteins will be validated for differential expression in primary cancer tissues, and evaluated for functional significance in esophageal adenocarcinoma cell lines. Novel biomarkers will be identified by integrated analysis of high throughput gene expression microarray and liquid chromatography/mass spectroscopy in tissue samples of esophageal adenocarcinoma. It is the goal of this training period to provide an intense research experience whereby expertise in genomic and proteomic analysis is gained leading to a career as an independent researcher and surgical oncologist. Environment: The outstanding and highly collaborative research environment at the University of Michigan and the Comprehensive Cancer Center will promote the accomplishment of this proposal. Candidate training and development will be directed by the dedicated mentorship and guidance of senior, accomplished scientists: David G. Beer, Ph.D. and David M. Lubman, Ph.D., both Professors in the Department of Surgery. The Chair of the Department of Surgery, Michael W. Mulholland, M.D., Ph.D., has had considerable experience in mentoring successful surgeon/scientists and has agreed to provide protected research time and career guidance to the candidate. Thus, this K08 funding period will allow the acquisition of new translational research skills leading to an independent cancer research career addressing a critically important clinical problem. Relevance: Identification and validation of potential biomarkers for response to chemotherapy ultimately can provide the clinician with additional means of providing specific, directed therapy for the individual patient.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Clinical Investigator Award (CIA) (K08)
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Subcommittee G - Education (NCI)
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Jakowlew, Sonia B
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University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
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Sheetz, K H; Zhao, L; Holcombe, S A et al. (2013) Decreased core muscle size is associated with worse patient survival following esophagectomy for cancer. Dis Esophagus 26:716-22
Chang, Andrew C; Lee, Julia S; Sawicki, Konrad T et al. (2010) Outcomes after esophagectomy in patients with prior antireflux or hiatal hernia surgery. Ann Thorac Surg 89:1015-21; discussion 1022-3
Silvers, Amy L; Lin, Lin; Bass, Adam J et al. (2010) Decreased selenium-binding protein 1 in esophageal adenocarcinoma results from posttranscriptional and epigenetic regulation and affects chemosensitivity. Clin Cancer Res 16:2009-21
Hartojo, Wibisono; Silvers, Amy L; Thomas, Dafydd G et al. (2010) Curcumin promotes apoptosis, increases chemosensitivity, and inhibits nuclear factor kappaB in esophageal adenocarcinoma. Transl Oncol 3:99-108
Zhu, Weijian; Appelman, Henry D; Greenson, Joel K et al. (2009) A histologically defined subset of high-grade dysplasia in Barrett mucosa is predictive of associated carcinoma. Am J Clin Pathol 132:94-100
Chang, Andrew C; Lee, Julia S (2009) Resection for esophageal cancer in the elderly. Thorac Surg Clin 19:333-43