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
485P - LDCT lung cancer screening of never-smokers meta-analysis subgroup analysis: Adenocarcinoma is the highly predictive histology identified in never-smokers
Presenter: Sai-Hong Ou
Session: Poster Display
Resources:
Abstract
486P - Fiscal feasibility and implications of integrating lung cancer screening into Hong Kong’s healthcare system
Presenter: Herbert Ho Fung Loong
Session: Poster Display
Resources:
Abstract
487P - Evaluating the performance of the USPSTF lung cancer screening guidelines in an Asian population of lung cancer patients
Presenter: Jian Wei Tan
Session: Poster Display
Resources:
Abstract
488P - Pulmonary ground glass opacity lesions: Immune ecosystem and its clinical relevances of early-stage lung adenocarcinoma
Presenter: Shensi Shen
Session: Poster Display
Resources:
Abstract
489TiP - BGB-LC-202 (NCT05577702): Phase II Umbrella study of tislelizumab (TIS) monotherapy and TIS-based immunotherapy combinations +/- chemotherapy (CT) as neoadjuvant treatment in Chinese patients (pts) with resectable stage II to IIIA non-small cell lung cancer (NSCLC)
Presenter: Wentao Yu
Session: Poster Display
Resources:
Abstract
491P - Furmonertinib as adjuvant therapy for elderly patients in resected EGFR-mutated non-small cell lung cancer: A double-center, real-world experience
Presenter: Ziheng Wu
Session: Poster Display
Resources:
Abstract
492P - Penpulimab-based combination neoadjuvant/adjuvant therapy for patients with resectable locally advanced non-small cell lung cancer: Preliminary results from a phase II study (ALTER-L043)
Presenter: Changli Wang
Session: Poster Display
Resources:
Abstract
493P - The prognostic value of 4L lymph node dissection in left-sided operable non-small cell lung cancer: A systematic review and meta-analysis
Presenter: Lei Peng
Session: Poster Display
Resources:
Abstract
495P - Intrinsic STING of CD8+T cells regulates self-metabolic reprogramming and exerts anti-tumor effects
Presenter: Qiuli Xu
Session: Poster Display
Resources:
Abstract
496P - Fruquintinib plus sintilimab in patients (pts) with advanced non-small cell lung cancer (NSCLC) with PD-L1-positive expression: A multicenter, single-arm phase II study
Presenter: Shun Lu
Session: Poster Display
Resources:
Abstract