Abstract 453P
Background
Radiation therapy and/or cetuximab treatments are commonly used in the treatment of head and neck cancers. A better understanding of mechanisms of resistance could enhance methods of circumventing resistance to these treatments. Furthermore, it will be helpful to better understand mechanisms by which cells become cross resistance to radiation and cetuximab.
Methods
In order to study resistance of human head and neck squamous cell cancers to cetuximab, we developed two cell lines with acquired resistance to cetuximab by continuous exposure to 5 μg/ml cetuximab for over 6 months (Biochem Biophys Res Comm 517(1):36-42, 2019, and PLoS ONE 15(2): e 0229077, 1-14, 2020). The two human head and neck squamous cell carcinoma cell lines were UM-SCC-1 and UM-SCC-6 and their cetuximab-resistant counterparts were UM-SCC-1R and UM-SCC-6R, respectively. Radiation resistance was assessed with a standard colony formation assay for cytotoxicity. DNA-double strand breaks (DSBs) were assessed by a standard neutral comet assay.
Results
Both cetuximab-resistant cell lines, UM-SCC-1R and UM-SCC6R, were resistant to radiation with colony formation assessments. This finding added to the previously reported radio-resistance noted by cell proliferation and apoptosis (ESMO Asia, 2023). Subsequently, radiation-induced DNA DSBs were assessed in the parental and cetuximab-resistant cell lines. It was determined that fewer radiation-induced DNA DSBs were noted in the UM-SCC-1R cells relative to the parental cells and this was true for repair times of 5 mins-4 hours. In contrast, these findings were not discovered in the UM-SCC-6R cells relative to parental cells. The time course of DNA DSB repair will be presented.
Conclusions
A reduction in radiation-induced DNA DSBs may play a role in cross-resistance to cetuximab and radiation in UM-SCC-1R cells, relative to parental cells, but does not appear to play the same role in UM-SCC-6R cells relative to parental cells. These findings suggest that cross resistance to cetuximab and radiation in human head and neck squamous cell cancer is multifactorial and may require tumor specific assessments in order to circumvent these processes.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
J. A. Bonner.
Funding
University of Alabama at Birmingham.
Disclosure
J.A. Bonner: Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor: Merck-Serono. All other authors have declared no conflicts of interest.