Cetuximab May Inhibit Tumor Growth and Angiogenesis Induced by Ionizing Radiation: A Preclinical Rationale for Maintenance Treatment After Radiotherapy.
Summary of "Cetuximab May Inhibit Tumor Growth and Angiogenesis Induced by Ionizing Radiation: A Preclinical Rationale for Maintenance Treatment After Radiotherapy."
Abstract Background. The benefits of radiotherapy and cetuximab have encouraged evaluation of cetuximab after radiotherapy. The aims of this study were to preclinically evaluate the efficacy of cetuximab maintenance after radiotherapy and eventually determine its mechanisms of action. Methods. The A431 human carcinoma cell line was treated in culture with fractionated radiotherapy and cetuximab. The surviving cells were injected s.c. into nude mice to mimic microscopic residual disease. The animals were randomized to receive either cetuximab or saline solution. Tumor growth, cell proliferation (Ki-67), microvessel density (MVD), epidermal growth factor receptor (EGFR) and transforming growth factor (TGF-alpha) mRNA transcription, and vascular endothelial growth factor (VEGF) secretion were measured. Results. Tumors from irradiated cells had a faster growth rate, higher Ki-67 index, and greater angiogenesis than tumors from untreated cells. This aggressive phenotype was associated with in vitro radiation-induced extracellular signal-related kinase (ERK)-1/2 and Akt activation, greater EGFR and TGF-alpha transcription, and augmented VEGF secretion, all of which were inhibited by cetuximab. In cetuximab-treated mice with tumors arising from irradiated cells, time to volume was longer by a factor of 3.52, whereas the Ki-67 index and MVD were 1.57 and 1.49 times lower, respectively, a larger enhancement than seen in tumors from untreated cells. These findings suggest that cells surviving radiation may express factors that promote cell survival and induce an aggressive phenotype that may potentially be blocked by cetuximab maintenance therapy. Conclusions. These results support the clinical evaluation of adjuvant therapy with cetuximab after radiotherapy in EGFR-dependent carcinomas.
Affiliation
IDIBELL, on behalf of Program of Applied Radiobiology of Catalonia (PRACAT).
Journal Details
This article was published in the following journal.
Name: The oncologist
ISSN: 1549-490X
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20798193
- DOI: http://dx.doi.org/10.1634/theoncologist.2008-0290
Medical and Biotech [MESH] Definitions
Abnormalities, Radiation-induced
Congenital changes in the morphology of organs produced by exposure to ionizing or non-ionizing radiation.
Leukemia, Radiation-induced
Leukemia produced by exposure to IONIZING RADIATION or NON-IONIZING RADIATION.
Neoplasms, Radiation-induced
Tumors, cancer or other neoplasms produced by exposure to ionizing or non-ionizing radiation.
Deinococcus
A genus of gram-positive aerobic cocci found in the soil, that is highly resistant to radiation, especially ionizing radiation (RADIATION, IONIZING). Deinococcus radiodurans is the type species.
Radiation Injuries, Experimental
Experimentally produced harmful effects of ionizing or non-ionizing RADIATION in CHORDATA animals.
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