1. Peginterferon Beta-1a Shows Antitumor Activity as a Single Agent and Enhances Efficacy of Standard of Care Cancer Therapeutics in Human Melanoma, Breast, Renal, and Colon Xenograft Models.
- Author
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Boccia A, Virata C, Lindner D, English N, Pathan N, Brickelmaier M, Hu X, Gardner JL, Peng L, Wang X, Zhang X, Yang L, Perron K, Yco G, Kelly R, Gamez J, Scripps T, Bennett D, Joseph IB, and Baker DP
- Subjects
- Animals, Antineoplastic Agents administration & dosage, Antineoplastic Agents pharmacokinetics, Antineoplastic Agents, Immunological pharmacology, Apoptosis drug effects, Biomarkers, Tumor, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Cell Line, Tumor, Cell Survival, Colonic Neoplasms drug therapy, Colonic Neoplasms pathology, Disease Models, Animal, Drug Therapy, Combination, Female, Humans, Interferon-beta administration & dosage, Interferon-beta pharmacokinetics, Kidney Neoplasms drug therapy, Kidney Neoplasms pathology, Male, Melanoma drug therapy, Melanoma pathology, Mice, Mice, Knockout, Mutation, Neoplasms genetics, Polyethylene Glycols administration & dosage, Polyethylene Glycols pharmacokinetics, Protein Kinase Inhibitors pharmacology, Treatment Outcome, Tumor Burden drug effects, Xenograft Model Antitumor Assays, Antineoplastic Agents pharmacology, Interferon-beta pharmacology, Neoplasms drug therapy, Neoplasms pathology, Polyethylene Glycols pharmacology
- Abstract
Because of its tumor-suppressive effect, interferon-based therapy has been used for the treatment of melanoma. However, limited data are available regarding the antitumor effects of pegylated interferons, either alone or in combination with approved anticancer drugs. We report that treatment of human WM-266-4 melanoma cells with peginterferon beta-1a induced apoptotic markers. Additionally, peginterferon beta-1a significantly inhibited the growth of human SK-MEL-1, A-375, and WM-266-4 melanoma xenografts established in immunocompromised mice. Peginterferon beta-1a regressed large, established WM-266-4 xenografts in nude mice. Treatment of SK-MEL-1 tumor-bearing mice with a combination of peginterferon beta-1a and the MEK inhibitor PD325901 ((R)-N-(2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzamide) significantly improved tumor growth inhibition compared with either agent alone. Examination of the antitumor activity of peginterferon beta-1a in combination with approved anticancer drugs in breast and renal carcinomas revealed improved antitumor activity in these preclinical xenograft models, as did the combination of peginterferon beta-1a and bevacizumab in a colon carcinoma xenograft model.
- Published
- 2017
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