Evidence map›Paper›PMID 42531323›Full record

ArticleCancer research communications2026

Combination AURKA and WEE1 Inhibition Exhibits Efficacy in EGFR or Pan-ERBB Inhibitor-Resistant Head and Neck Squamous Cell Carcinoma.

Flaviane N Silva, Jong Woo Lee, Theodore T Nguyen, Fiona M Goeckel, Tetyana Bagnyukova, Hossein Borghaei, Erica A Golemis, Barbara A Burtness

Abstract read
In one paragraph

Article in Cancer research communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Flaviane N Silva *Cancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.ORCID 0000-0003-3778-1800
Jong Woo Lee *Section of Medical Oncology, Department of Internal Medicine, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut.ORCID 0000-0002-8352-4269
Theodore T NguyenCancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.ORCID 0009-0007-9568-6699
Fiona M GoeckelChestnut Hill College, Philadelphia, Pennsylvania.ORCID 0009-0005-3726-0409
Tetyana BagnyukovaCancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.ORCID 0009-0005-6825-2313
Hossein BorghaeiCancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.ORCID 0000-0002-2577-4454
Erica A GolemisCancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.ORCID 0000-0003-3618-3673
Barbara A BurtnessSection of Medical Oncology, Department of Internal Medicine, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut.ORCID 0000-0003-4660-1859

Funding

WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Eric Andrew Ross · 1985 to 2026
$138.8M
Yale Head and Neck Cancer SPORE: Overcoming Treatment Resistance in Head and Neck CancerP50DE030707 · NIDCR · YALE UNIVERSITY · PI BURTNESS, BARBARA · 2020 to 2024
$11.8M
National Cancer Institute (NCI) CA006927National Institute of Dental and Craniofacial Research (NIDR) DE030707NCI NIH HHS P30 CA006927NIDCR NIH HHS P50 DE030707U.S. Department of Defense (DOD) CA201045
6 · The paper itself

Abstract

More than 600,000 cases of head and neck squamous cell carcinoma (HNSCC) are diagnosed globally each year. Many HNSCCs overexpress the ERBB family member epidermal growth factor receptor (EGFR), and EGFR inhibitors (EGFRi) and pan-ERBB inhibitors (ERBBi) are clinically active in the treatment of locally advanced, metastatic, or recurrent HNSCC. However, resistance to these inhibitors typically develops, often associated with epithelial-mesenchymal transition (EMT). Aurora kinase A (AURKA), a mitotic regulator with expanded signaling functions in tumors, has been reported to reverse EGFR resistance in EGFR-mutated lung cancer. To identify strategies to overcome resistance in HNSCC, we developed HNSCC cell models that were treatment-naïve parental or selected for resistance to the EGFRi erlotinib or the ERBBi afatinib. The resistant HNSCC models had typically undergone partial EMT, consistent with clinical resistance, associated with upregulation of the AURKA partner protein NEDD9. Synergy of the AURKA inhibitor VIC-1911 with erlotinib or afatinib in parental models was reduced in resistant models in short-term growth assays. In longer-term clonogenic assays and in vivo, cells selected for EGFRi/ERBBi resistance showed heightened sensitivity to VIC-1911, contributing to reduced synergy. Based on increased AURKA dependence, we compared the combination of VIC-1911 with adavosertib, an inhibitor of the cell-cycle checkpoint regulator WEE1, in parental and resistant models. These showed a combination effect both in vitro and in vivo that was retained in ERBBi-resistant xenografts, suggesting the potential value of combined AURKA and WEE1 inhibitor use in patients with ERBBi-resistant HNSCC. SIGNIFICANCE: Treatment resistance is a major source of mortality for HNSCC. This study investigates strategies to overcome resistance to inhibitors of the ERBB family, which are commonly used for the treatment of advanced HNSCC. The results suggest the value of the use of combined AURKA and WEE inhibition in the resistance setting.

Indexed as

Aurora Kinase ACell Cycle ProteinsDrug Resistance, NeoplasmHead and Neck NeoplasmsProtein Kinase InhibitorsSquamous Cell Carcinoma of Head and NeckAnimalsCell Line, TumorEpithelial-Mesenchymal TransitionErbB ReceptorsErlotinib HydrochlorideFemaleHumansMiceNuclear ProteinsProtein-Tyrosine KinasesadavosertibAURKA protein, humanAurora Kinase ACell Cycle ProteinsEGFR protein, humanErbB ReceptorsErlotinib HydrochlorideNuclear ProteinsProtein Kinase InhibitorsProtein-Tyrosine KinasesPyrazolesPyrimidinesPyrimidinonesWEE1 protein, human

Identifiers

PMID42531323
PMCPMC13489673

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.