The Role of Akt in Acquired Cetuximab Resistant Head and Neck Squamous Cell Carcinoma: An In Vitro Study on a Novel Combination Strategy Article Swipe
Hannah Zaryouh
,
Ines De Pauw
,
Hasan Baysal
,
Patrick Pauwels
,
Marc Peeters
,
Jan B. Vermorken
,
Filip Lardon
,
An Wouters
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3389/fonc.2021.697967
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3389/fonc.2021.697967
The epidermal growth factor receptor (EGFR) is a therapeutic target in head and neck squamous cell carcinoma (HNSCC). Resistance to EGFR-targeted therapies, such as cetuximab, poses a challenging problem. This study aims to characterize acquired cetuximab resistance mechanisms in HNSCC cell lines by protein phosphorylation profiling. Through this, promising combination treatments can be identified to possibly overcome acquired cetuximab resistance in HNSCC. Protein phosphorylation profiling showed increased phosphorylation of Akt1/2/3 after cetuximab treatment in acquired cetuximab resistant cells compared to cetuximab sensitive cells, which was confirmed by western blotting. Based on this protein phosphorylation profile, a novel combination treatment with cetuximab and the Akt1/2/3 inhibitor MK2206 was designed. Synergy between cetuximab and MK2206 was observed in two cetuximab sensitive HNSCC cell lines and one acquired cetuximab resistant variant in simultaneous treatment schedules. In conclusion, this study demonstrates that increased Akt1/2/3 phosphorylation seems to be characteristic for acquired cetuximab resistance in HNSCC cell lines. Our results also show an additive to synergistic interaction between cetuximab and MK2206 in simultaneous treatment schedules. These data support the hypothesis that the combination of cetuximab with PI3K/Akt pathway inhibition might be a promising novel therapeutic strategy to overcome acquired cetuximab resistance in HNSCC patients.
Related Topics
Concepts
Cetuximab
Head and neck squamous-cell carcinoma
Cancer research
Protein kinase B
Medicine
EGFR inhibitors
AKT1
Epidermal growth factor receptor
PI3K/AKT/mTOR pathway
Phosphorylation
Oncology
Head and neck cancer
Internal medicine
Radiation therapy
Cancer
Signal transduction
Chemistry
Colorectal cancer
Biochemistry
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fonc.2021.697967
- OA Status
- gold
- Cited By
- 17
- References
- 63
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3201171647
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3201171647Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3389/fonc.2021.697967Digital Object Identifier
- Title
-
The Role of Akt in Acquired Cetuximab Resistant Head and Neck Squamous Cell Carcinoma: An In Vitro Study on a Novel Combination StrategyWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-09-10Full publication date if available
- Authors
-
Hannah Zaryouh, Ines De Pauw, Hasan Baysal, Patrick Pauwels, Marc Peeters, Jan B. Vermorken, Filip Lardon, An WoutersList of authors in order
- Landing page
-
https://doi.org/10.3389/fonc.2021.697967Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.3389/fonc.2021.697967Direct OA link when available
- Concepts
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Cetuximab, Head and neck squamous-cell carcinoma, Cancer research, Protein kinase B, Medicine, EGFR inhibitors, AKT1, Epidermal growth factor receptor, PI3K/AKT/mTOR pathway, Phosphorylation, Oncology, Head and neck cancer, Internal medicine, Radiation therapy, Cancer, Signal transduction, Chemistry, Colorectal cancer, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
17Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 2, 2024: 4, 2023: 5, 2022: 6Per-year citation counts (last 5 years)
- References (count)
-
63Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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