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Published on: April 22, 2019
Predictive Value of EGFR-PI3K-AKT-mTOR-Pathway Inhibitor Biomarkers for Head and Neck Squamous Cell Carcinoma: A
W W B de Kort1, S Spelier2, L A Devriese3
1Department of Pathology, University Medical Center Utrecht, PO Box 885500, 3508 GA, Utrecht, The Netherlands. W.W.B.dekort-3@umcutrecht.nl.
Background:
Understanding molecular pathogenesis of head and neck squamous cell carcinomas (HNSCC) has considerably improved in the last decades. As a result, novel therapeutic strategies have evolved, amongst which are epidermal growth factor receptor (EGFR)-targeted therapies. With the exception of cetuximab, targeted therapies for HNSCC have not yet been introduced into clinical practice. One important aspect of new treatment regimes in clinical practice is presence of robust biomarkers predictive for therapy response.
Methods:
We performed a systematic search in PubMed, Embase and the Cochrane library. Articles were included if they investigated a biomarker for targeted therapy in the EGFR-PI3K-AKT-mTOR-pathway.
Results:
Of 83 included articles, 52 were preclinical and 33 were clinical studies (two studies contained both a preclinical and a clinical part). We classified EGFR pathway inhibitor types and investigated the type of biomarker (biomarker on epigenetic, DNA, mRNA or protein level).
Conclusion:
Several EGFR-PI3K-AKT-mTOR-pathway inhibitor biomarkers have been researched for HNSCC but few of the investigated biomarkers have been adequately confirmed in clinical trials. A more systematic approach is needed to discover proper biomarkers as stratifying patients is essential to prevent unnecessary costs and side effects.
Insights
Biomarkers for targeted therapies in head and neck squamous cell carcinomas (HNSCC) are crucial for effective treatment. However, few biomarkers targeting the EGFR-PI3K-AKT-mTOR pathway have been validated in clinical trials for HNSCC.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Head and neck squamous cell carcinomas (HNSCC) research has advanced understanding of molecular pathogenesis.
- Epidermal growth factor receptor (EGFR)-targeted therapies are emerging as novel treatment strategies for HNSCC.
- Robust biomarkers predicting response to targeted therapies are essential for clinical implementation.
Approach:
- A systematic literature search was conducted across PubMed, Embase, and the Cochrane library.
- Studies investigating biomarkers for targeted therapy within the EGFR-PI3K-AKT-mTOR pathway were included.
- Biomarkers were classified based on their molecular level (epigenetic, DNA, mRNA, or protein).
Key Points:
- The review encompassed 83 articles, comprising 52 preclinical and 33 clinical studies.
- Various biomarkers for EGFR-PI3K-AKT-mTOR pathway inhibitors in HNSCC have been explored.
- A significant gap exists between researched biomarkers and those confirmed through clinical trials.
Conclusions:
- Few biomarkers for targeted therapy in HNSCC have demonstrated sufficient clinical validation.
- A more systematic approach is required for biomarker discovery and validation in HNSCC.
- Patient stratification using reliable biomarkers is vital to optimize treatment efficacy and minimize costs and side effects.
