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Updated: Oct 26, 2025
Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
Published on: April 20, 2018
Precision Medicine Gains Momentum: Novel 3D Models and Stem Cell-Based Approaches in Head and Neck Cancer
Annette Affolter1, Anne Lammert1, Johann Kern1
1Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Abstract:
Despite the current progress in the development of new concepts of precision medicine for head and neck squamous cell carcinoma (HNSCC), in particular targeted therapies and immune checkpoint inhibition (CPI), overall survival rates have not improved during the last decades. This is, on the one hand, caused by the fact that a significant number of patients presents with late stage disease at the time of diagnosis, on the other hand HNSCC frequently develop therapeutic resistance. Distinct intratumoral and intertumoral heterogeneity is one of the strongest features in HNSCC and has hindered both the identification of specific biomarkers and the establishment of targeted therapies for this disease so far. To date, there is a paucity of reliable preclinical models, particularly those that can predict responses to immune CPI, as these models require an intact tumor microenvironment (TME). The "ideal" preclinical cancer model is supposed to take both the TME as well as tumor heterogeneity into account. Although HNSCC patients are frequently studied in clinical trials, there is a lack of reliable prognostic biomarkers allowing a better stratification of individuals who might benefit from new concepts of targeted or immunotherapeutic strategies. Emerging evidence indicates that cancer stem cells (CSCs) are highly tumorigenic. Through the process of stemness, epithelial cells acquire an invasive phenotype contributing to metastasis and recurrence. Specific markers for CSC such as CD133 and CD44 expression and ALDH activity help to identify CSC in HNSCC. For the majority of patients, allocation of treatment regimens is simply based on histological diagnosis and on tumor location and disease staging (clinical risk assessments) rather than on specific or individual tumor biology. Hence there is an urgent need for tools to stratify HNSCC patients and pave the way for personalized therapeutic options. This work reviews the current literature on novel approaches in implementing three-dimensional (3D) HNSCC in vitro and in vivo tumor models in the clinical daily routine. Stem-cell based assays will be particularly discussed. Those models are highly anticipated to serve as a preclinical prediction platform for the evaluation of stable biomarkers and for therapeutic efficacy testing.
Insights
Precision medicine for head and neck squamous cell carcinoma (HNSCC) needs better preclinical models. Three-dimensional (3D) and stem-cell based assays show promise for predicting treatment response and identifying biomarkers.
Area of Science:
- Oncology
- Translational Medicine
- Cancer Research
Background:
- Head and neck squamous cell carcinoma (HNSCC) survival rates have stagnated despite advances in precision medicine, including targeted therapies and immune checkpoint inhibition (CPI).
- Therapeutic resistance and significant intratumoral/intertumoral heterogeneity in HNSCC impede biomarker identification and targeted therapy development.
- Current preclinical models often lack the necessary tumor microenvironment (TME) complexity to accurately predict responses to immunotherapies like CPI.
Purpose of the Study:
- To review novel approaches for implementing three-dimensional (3D) HNSCC in vitro and in vivo tumor models in clinical practice.
- To highlight the potential of stem-cell based assays in addressing the limitations of current HNSCC research models.
- To explore the utility of these advanced models for evaluating biomarkers and therapeutic efficacy.
Main Methods:
- Literature review of current research on 3D HNSCC models (in vitro and in vivo).
- Focus on stem-cell based assays and their role in cancer stem cell (CSC) identification (e.g., CD133, CD44, ALDH activity).
- Discussion of how these models incorporate TME and tumor heterogeneity.
Main Results:
- Existing preclinical models for HNSCC often fail to capture crucial aspects of tumor biology, such as heterogeneity and TME.
- Cancer stem cells (CSCs) are identified as key drivers of tumorigenicity, metastasis, and recurrence in HNSCC.
- 3D and stem-cell based models offer a more biologically relevant platform for HNSCC research compared to traditional 2D cultures.
Conclusions:
- There is an urgent need for improved preclinical models to stratify HNSCC patients and guide personalized therapeutic strategies.
- Three-dimensional (3D) HNSCC models, particularly those incorporating stem-cell based assays, are promising for predicting treatment responses.
- These advanced models are anticipated to serve as critical platforms for the evaluation of novel biomarkers and therapeutic efficacy testing in HNSCC.
