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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.
- Source :
-
Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research [J Interferon Cytokine Res] 2017 Jan; Vol. 37 (1), pp. 20-31. Date of Electronic Publication: 2016 Nov 11. - Publication Year :
- 2017
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1557-7465
- Volume :
- 37
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
- Publication Type :
- Academic Journal
- Accession number :
- 27835061
- Full Text :
- https://doi.org/10.1089/jir.2016.0027