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Updated: Sep 21, 2025
Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
Published on: April 20, 2018
Preclinical Head and Neck Squamous Cell Carcinoma Models for Combined Targeted Therapy Approaches
Nina Schoenwaelder1, Mareike Krause1, Thomas Freitag1
1Hematology, Oncology, Palliative Medicine, Department of Medicine, Clinic III, Rostock University Medical Center, 18057 Rostock, Germany.
Abstract:
This study aimed to refine combined targeted approaches on well-characterized, low-passage tumor models. Upon in vivo xenografting in immunodeficient mice, three cell lines from locally advanced or metastatic HNSCC were established. Following quality control and basic characterization, drug response was examined after therapy with 5-FU, Cisplatin, and cyclin-dependent kinase inhibitors (abemaciclib, THZ1). Our cell lines showed different in vitro growth kinetics, morphology, invasive potential, and radiosensitivity. All cell lines were sensitive to 5-FU, Cisplatin, and THZ1. One cell line (HNSCC48 P0 M1) was sensitive to abemaciclib. Here, Cyto-FISH revealed a partial CDKN2a deletion, which resulted from a R58* mutation. Moreover, this cell line demonstrated chromosome 12 polysomy, accompanied by an increase in CDK4-specific copy numbers. In HNSCC16 P1 M1, we likewise identified polysomy-associated CDK4-gains. Although not sensitive to abemaciclib per se, the cell line showed a G1-arrest, an increased number of acidic organelles, and a swollen structure. Notably, intrinsic resistance was conquered by Cisplatin because of cMYC and IDO-1 downregulation. Additionally, this Cisplatin-CDKI combination induced HLA-ABC and PD-L1 upregulation, which may enhance immunogenicity. Performing functional and molecular analysis on patient-individual HNSCC-models, we identified CDK4-gains as a biomarker for abemaciclib response prediction and describe an approach to conquer intrinsic CDKI resistance.
Insights
Researchers developed patient-specific head and neck cancer models to test targeted therapies. CDK4 gains were identified as a biomarker for abemaciclib response, and strategies to overcome resistance were explored.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Head and neck squamous cell carcinoma (HNSCC) presents challenges in treatment due to its heterogeneity.
- Developing well-characterized, patient-derived models is crucial for refining targeted therapeutic strategies.
Purpose of the Study:
- To establish and characterize low-passage HNSCC tumor models for drug response evaluation.
- To investigate the efficacy of 5-FU, Cisplatin, and cyclin-dependent kinase inhibitors (abemaciclib, THZ1).
- To identify predictive biomarkers and overcome intrinsic drug resistance in HNSCC.
Main Methods:
- In vivo xenografting of HNSCC cell lines in immunodeficient mice.
- In vitro drug sensitivity assays with 5-FU, Cisplatin, abemaciclib, and THZ1.
- Cyto-FISH for genetic analysis (CDKN2a deletion, CDK4 copy number).
- Functional and molecular analyses to assess drug resistance mechanisms.
Main Results:
- Established three distinct HNSCC cell lines with varying characteristics.
- All models showed sensitivity to 5-FU, Cisplatin, and THZ1; one model responded to abemaciclib.
- CDK4 gains identified as a biomarker for abemaciclib response prediction.
- Cisplatin overcame intrinsic resistance by downregulating cMYC and IDO-1, enhancing immunogenicity via HLA-ABC and PD-L1 upregulation.
Conclusions:
- Patient-derived HNSCC models are valuable tools for therapeutic strategy refinement.
- CDK4 copy number gains predict response to abemaciclib in HNSCC.
- Combined therapies, like Cisplatin with CDKIs, can overcome resistance and potentially enhance anti-tumor immunity.
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