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Updated: May 28, 2025
05:45
In Vitro Establishment of a Genetically Engineered Murine Head and Neck Cancer Cell Line using an Adeno-Associated Virus-Cas9 System
Published on: January 9, 2020
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RAC1-Amplified and RAC1-A159V Hotspot-Mutated Head and Neck Cancer Sensitive to the Rac Inhibitor EHop-016 In Vivo: A
Helen Hoi Yin Chan1, Hoi-Lam Ngan1, Yuen-Keng Ng2,3
1School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Cancers
|February 13, 2025
Summary
Genomic aberrations in RAC1 drive head and neck squamous cell carcinoma (HNSCC) growth. Targeting RAC1 with EHop-016 shows promise for precision medicine in HNSCC and other cancers.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- RAC1 aberrations are common in head and neck squamous cell carcinoma (HNSCC) but are currently not targetable for treatment.
- Specific RAC1 mutations (A159V, P29S) and copy number increases are linked to poor survival in HPV-negative HNSCC patients.
Purpose of the Study:
- To investigate the clinical significance of RAC1 genomic aberrations in HNSCC.
- To explore the potential of targeting RAC1 for cancer therapy.
Main Methods:
- Analysis of TCGA-HNSCC data for correlations between RAC1 aberrations and patient survival.
- In vitro and in vivo studies using HNSCC patient-derived xenografts (PDXs) and engineered models to assess the functional impact of RAC1 aberrations.
- Transcriptomic analysis to understand pathway activation.
- Proof-of-principle drug targeting using EHop-016.
Main Results:
- RAC1 aberrations (A159V, P29S mutations, copy number increases) significantly drive HNSCC tumor growth and invasion.
- RAC1 aberrations activate the PI3K pathway, with A159V mutants showing increased phospho-RPS6 levels.
- EHop-016 demonstrated significant antitumor activity against RAC1-aberrant HNSCC, melanoma, and endometrial cancer models.
Conclusions:
- RAC1 genomic aberrations represent actionable targets in HNSCC.
- Targeting RAC1 with drugs like EHop-016 offers a potential precision medicine strategy for HNSCC and other cancers with RAC1 alterations.
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