We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Small molecule profiling to define synergistic EGFR inhibitor combinations in head and neck squamous cell carcinoma.
- Authors
Michmerhuizen, Nicole L.; Ludwig, Megan L.; Birkeland, Andrew C.; Nimmagadda, Sai; Zhai, Jingyi; Wang, Jiayu; Jewell, Brittany M.; Genouw, Dylan; Remer, Lindsay; Kim, Daniel; Foltin, Susan K.; Bhangale, Apurva; Kulkarni, Aditi; Bradford, Carol R.; Swiecicki, Paul L.; Carey, Thomas E.; Jiang, Hui; Brenner, J. Chad
- Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) is a debilitating disease with poor survival. Although epidermal growth factor receptor (EGFR)‐targeting antibody cetuximab improves survival in some settings, responses are limited suggesting that alternative approaches are needed. Methods: We performed a high throughput drug screen to identify EGFR inhibitor‐based synergistic combinations of clinically advanced inhibitors in models resistant to EGFR inhibitor monotherapies, and then performed downstream validation experiments on prioritized synergistic combinations. Results: From our screen, we re‐discovered known synergistic EGFR inhibitor combinations with FGFR or IGF‐1R inhibitors that were broadly effective and also discovered novel synergistic combinations with XIAP inhibitor and DNMT inhibitors that were effective in only a subset of models. Conclusions: Conceptually, our data identify novel synergistic combinations that warrant evaluation in future studies, and suggest that some combinations, although highly synergistic, will require parallel companion diagnostic development to be effectively advanced in patients.
- Subjects
CETUXIMAB; SMALL molecules; SQUAMOUS cell carcinoma; EPIDERMAL growth factor receptors; HIGH throughput screening (Drug development)
- Publication
Head & Neck, 2022, Vol 44, Issue 5, p1192
- ISSN
1043-3074
- Publication type
Article
- DOI
10.1002/hed.27018