Jamie N Hadac1, Devon D Miller2, Ian C Grimes2, Linda Clipson1, Michael A Newton3, William R Schelman4, Richard B Halberg5. 1. Department of Oncology, K4/532 Clinical Science Center, Madison, WI, U.S.A. 2. Department of Medicine, Division of Gastroenterology and Hepatology, K4/532 Clinical Science Center, Madison, WI, U.S.A. 3. Departments of Statistics and of Biostatistics and Medical Informatics, 1245a, K6/434 Medical Sciences Center, Madison, WI, U.S.A. 4. Department of Medicine, Division of Hematology and Oncology, K4/532 Clinical Science Center, Madison, WI, U.S.A. 5. Department of Medicine, Division of Gastroenterology and Hepatology, K4/532 Clinical Science Center, Madison, WI, U.S.A. Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, U.S.A. rbhalberg@medicine.wisc.edu.
Abstract
BACKGROUND: Despite receiving post-operative 5-fluorouracil (5-FU)-based chemotherapy, approximately 50% of patients with stage IIIC colon cancer experience recurrence. Currently, no molecular signature can predict response to 5-FU. MATERIALS AND METHODS: Mouse models of colon cancer have been developed and characterized. Individual tumors in these mice can be longitudinally monitored and assessed to identify differences between those that are responsive and those that are resistant to therapy. Gene expression was analyzed in serial biopsies that were collected before and after treatment with 5-FU. Colon tumors had heterogeneous responses to treatment with 5-FU. Microarray analysis of pre-treatment biopsies revealed that Hp1bp3, a gene encoding heterochromatin protein 1 binding protein 3, was differentially expressed between sensitive and resistant tumors. CONCLUSION: Using mouse models of human colorectal cancer, Hp1bp3 was identified as a candidate marker of intrinsic 5-FU resistance and may represent a potential biomarker for patient stratification or a target of clinical importance. Copyright
BACKGROUND: Despite receiving post-operative 5-fluorouracil (5-FU)-based chemotherapy, approximately 50% of patients with stage IIIC colon cancer experience recurrence. Currently, no molecular signature can predict response to 5-FU. MATERIALS AND METHODS:Mouse models of colon cancer have been developed and characterized. Individual tumors in these mice can be longitudinally monitored and assessed to identify differences between those that are responsive and those that are resistant to therapy. Gene expression was analyzed in serial biopsies that were collected before and after treatment with 5-FU. Colon tumors had heterogeneous responses to treatment with 5-FU. Microarray analysis of pre-treatment biopsies revealed that Hp1bp3, a gene encoding heterochromatin protein 1 binding protein 3, was differentially expressed between sensitive and resistant tumors. CONCLUSION: Using mouse models of humancolorectal cancer, Hp1bp3 was identified as a candidate marker of intrinsic 5-FU resistance and may represent a potential biomarker for patient stratification or a target of clinical importance. Copyright
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