389P - Lack of cross-resistance to erlotinib in human head and neck cancer cells with acquired resistance to cetuximab

Background

Patients with head and neck cancers often require multimodality treatments. Therefore, cross-resistance to various treatments that are employed for these patients poses a significant therapeutic problem. A better understanding of therapeutic cross-resistance could lead to methods which will circumvent cross-resistance. Herein, we explore erlotinib (anti-EGFr, TKI) and radiation sensitivity in human head and neck cancer cells with acquired resistance to cetuximab (anti-EGFr mAb).

Methods

Two human head and neck squamous cell cancers were utilized for these for these studies; UM-SCC-1 and UM-SCC-6. It has been previously reported that UM-SCC-1 is substantially more radioresistant than UM-SCC-6 (IJROBP 29 (2):243-247,1994). We have previously reported on cell lines that were created by continuous exposure of the above cell lines to 5 μg/ml cetuximab (Biochem Biophys Res Common 517(1): 36-42, 2019 and PLoS ONE 15(2) eo229077,1-14, 2020). Therefore, two cetuximab-resistant cell lines were created; UM-SCC-1R and UM-SCC-6R. Radiation sensitivity and erlotinib sensitivity were investigated through the use of standard proliferation assays and apoptosis assays as previously described (BMC Cancer 15:673, 2015).

Results

For the assessments of radiation sensitivity and erlotinib sensitivity, comparisons were made between the two cetuximab-resistant cell lines (UM-SCC-1R and UM-SCC-6R) with their respective parental cell lines (UM-SCC-1 and UM-SCC-6). It was discovered that the two cetuximab resistant cell lines were also radioresistant relative to their respective parental lines, regarding cell proliferation and apoptosis. However, the two cetuximab resistant cell lines were not cross-resistant to erlotinib.

Conclusions

Acquired resistance to cetuximab was found to correlate with radiation-resistance but not erlotinib-resistance. Since cetuximab is an anti-EGFr monoclonal antibody and erlotinib is an anti-EGFr tyrosine kinase inhibitor, further studies are underway to investigate the role of downstream signaling events that may contribute to our understanding for the lack of cross-resistance between cetuximab and erlotinib.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

J. A. Bonner.

Funding

Has not received any funding.

Disclosure

J.A. Bonner: Financial Interests, Personal, Advisory Board: Merck Serono. All other authors have declared no conflicts of interest.