Abstract 389P
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.
Resources from the same session
497P - Sintilimab in combination with anlotinib in advanced NSCLC treated with first-line PD-1 antibodies: An open, single-arm, phase II trial
Presenter: Ying Jin
Session: Poster Display
Resources:
Abstract
498P - Frailty-adjusted life expectancy and survival in older lung cancer patients: A large-scale electronic health-record based study
Presenter: Thao Tu
Session: Poster Display
Resources:
Abstract
499P - Long-term survival and treatment (tx) patterns after first-line (1L) osimertinib in patients (pts) with epidermal growth factor receptor (EGFR) mutation-positive (m) advanced non-small cell lung cancer (NSCLC): Japanese cohort of a global real-world (rw) observational study
Presenter: Daichi Fujimoto
Session: Poster Display
Resources:
Abstract
500P - The effectiveness and safety of durvalumab after chemoradiotherapy for locoregional recurrence of completely resected non-small cell lung cancer: Real-world, multicenter, observational study (NEJ056)
Presenter: Hidehito Horinouchi
Session: Poster Display
Resources:
Abstract
501P - One-year survival outcomes of unresectable stage III non-small cell lung cancer patients who underwent PD-1 inhibitor plus chemo as induction therapy
Presenter: Xin Wang
Session: Poster Display
Resources:
Abstract
502P - Impact of sarcopenia on the outcome of patients with locally advanced non-small cell lung cancer treated with chemoradiotherapy followed by durvalumab
Presenter: Kentaro Tamura
Session: Poster Display
Resources:
Abstract
503P - Clinical outcomes by infusion timing of immune checkpoint inhibitors in patients with locally advanced NSCLC
Presenter: TSUYOSHI HIRATA
Session: Poster Display
Resources:
Abstract
504P - Real-world outcomes with induction systemic therapy for stage III in eligible for upfront local therapy: Pre vs post immunotherapy era in a tertiary referral centre
Presenter: Praveen Kumar Marimuthu
Session: Poster Display
Resources:
Abstract
505P - Neoadjuvant PD-1 inhibitor (tislelizumab) plus platinum–etoposide in patients with limited-stage small cell lung cancer: A phase II trial
Presenter: Junjie Hu
Session: Poster Display
Resources:
Abstract
506P - Intrathoracic progression is still the most dominant failure pattern after first-line chemo-immunotherapy in extensive-stage small-cell lung cancer: Implications for thoracic radiotherapy
Presenter: Byoung Hyuck Kim
Session: Poster Display
Resources:
Abstract