Details

Autor(en) / Beteiligte

• Li, Hua
• Peyser, Noah D
• Zeng, Yan
• Ha, Patrick K
• Johnson, Daniel E
• Grandis, Jennifer R

Titel

NSAIDs Overcome PIK3CA Mutation-Mediated Resistance to EGFR Inhibition in Head and Neck Cancer Preclinical Models

Ist Teil von

• Cancers, 2022-01, Vol.14 (3), p.506

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2022

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Epidermal growth factor receptor (EGFR) inhibitors are approved by the Food and Drug Administration (FDA) but remain under active clinical investigation for the treatment of both newly diagnosed and recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Despite EGFR expression in the majority of HNSCC tumors, the levels of total or phosphorylated EGFR have not consistently been correlated with a response to EGFR targeting agents. The lack of predictive biomarkers represents a major obstacle to successful use of these drugs. Activation of phosphatidylinositol 3-kinase (PI3K) signaling by mutation of the oncogene represents a plausible mechanism for EGFR inhibitor drug resistance. We compared the impact of EGFR inhibitors, alone or in combination with non-steroidal anti-inflammatory drugs (NSAIDs), in preclinical HNSCC models harboring mutant versus wild-type . Our results demonstrate additive or synergistic effects of NSAIDs and EGFR inhibitors in vitro and in vivo in -mutated HNSCC models. These findings suggest that the addition of NSAIDs to EGFR inhibitors for the treatment of HNSCC may represent a promising therapeutic strategy in -mutated cancers.