Prevention Of Spontaneous Tumors By Pharmacological Inhibition Of The Epidermal Growth Factor Receptor
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Abstract
The epidermal growth factor receptor (EGFR) is a ligand-activated tyrosine kinase receptor that is often overexpressed in cancers and plays a significant role in cell proliferation and inhibition of apoptosis. Mouse model studies have demonstrated the ability of EGFR inhibition to hinder spontaneous colorectal cancer occurrence by 50-80% when EGFR inhibition is induced before the establishment of tumors (Rinella, ES and Threadgill, DW doi 10.1371/journal.pone.0039552). The success rates reported in human clinical trials differ from mouse model studies, with a 15% success rate among colorectal cancer patients receiving anti-EGFR treatment (Pritchart CC, and Grady WM doi 10.1136/gut.2009.206250). Timing of treatment is the major difference between animal/mouse trials and human therapeutic treatment of end-stage cancers. In our study, it was hypothesized that earlier preventative doses of the AG1478 chemotherapy inhibitor would reduce the frequency of spontaneous tumor occurrence in a preventative, rather than therapeutic, manner in a murine population. This current study provides additional specificity and histopathological analysis of the spontaneous tumor occurrence in a large murine sample of four genetically distinct wild-type strain mice to better simulate a variable human population. Such specificity includes, but is not limited to, the number, type and severity of the tumors that did occur and whether the concentration of the drug is correlated to a reduction in tumor occurrence. Such information will broaden the discussion of EGFR’s role in tumor treatment.
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EGFR, EGFR inhibition, Chemotherapy, Preventative Chemotherapy, Tumor treatment, Murine, Murine Tumor, Epidermal Growth Factor, AG1478, Tyrphostin AG1478, AG1478 inhibitor, AG1478 efficacy, Efficacy, Histology, Histopathology, Histopathological, Adenoma, Pulmonary adenoma, Hyperplasia, White pulp hyperplasia, Hypoplasia, White pulp hypoplasia, Sarcoma, Soft tissue sarcoma