Preclinical models of head and neck squamous cell carcinoma for a basic understanding of cancer biology and its translation into efficient therapies

Tinhofer, Ingeborg; Braunholz, Diana; Klinghammer, Konrad

doi:10.1186/s41199-020-00056-4

Cited by 29 publications

(32 citation statements)

References 70 publications

(119 reference statements)

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“…Furthermore, the response of organoids to radiation in these ex vivo models also correlated with the response observed in matched patients [40,41], and can be used to test the feasibility of new radiotherapeutic approaches [9]. Importantly, unwanted side-effects in normal tissues can also be studied in organoid models [45]. These adverse drug reactions are a major clinical problem, limiting the dose and effectiveness of drugs.…”

Section: Drug Screening Using Organoidsmentioning

confidence: 92%

Patient-Derived Organoids as a Model for Cancer Drug Discovery

Rae

Amato

Braconi

2021

IJMS

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In the search for the ideal model of tumours, the use of three-dimensional in vitro models is advancing rapidly. These are intended to mimic the in vivo properties of the tumours which affect cancer development, progression and drug sensitivity, and take into account cell–cell interactions, adhesion and invasiveness. Importantly, it is hoped that successful recapitulation of the structure and function of the tissue will predict patient response, permitting the development of personalized therapy in a timely manner applicable to the clinic. Furthermore, the use of co-culture systems will allow the role of the tumour microenvironment and tissue–tissue interactions to be taken into account and should lead to more accurate predictions of tumour development and responses to drugs. In this review, the relative merits and limitations of patient-derived organoids will be discussed compared to other in vitro and ex vivo cancer models. We will focus on their use as models for drug testing and personalized therapy and how these may be improved. Developments in technology will also be considered, including the use of microfluidics, 3D bioprinting, cryopreservation and circulating tumour cell-derived organoids. These have the potential to enhance the consistency, accessibility and availability of these models.

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Section: Drug Screening Using Organoidsmentioning

confidence: 92%

Patient-Derived Organoids as a Model for Cancer Drug Discovery

Rae

Amato

Braconi

2021

IJMS

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“…The poor prognosis of HNSCC patients is due to limited treatment modalities. In recent years the knowledge concerning HNSCC biology and the role of immune escape has expand significantly (Huang et al 2021 ; Tinhofer et al 2020 ). As a result, the development of novel and promising therapeutic immune approaches is crucial for HNSCC patients.…”

Section: The Traditional Treatment Of Hnsccmentioning

confidence: 99%

Head and Neck Squamous Cell Carcinoma: Risk Factors, Molecular Alterations, Immunology and Peptide Vaccines

Sun

Chen

et al. 2021

Int J Pept Res Ther

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Head and neck squamous cell carcinoma (HNSCC) arises from the epithelial lining of the oral cavity, hypopharynx, oropharynx, and larynx. There are several potential risk factors that cause the generation of HNSCC, including cigarette smoking, alcohol consumption, betel quid chewing, inadequate nutrition, poor oral hygiene, HPV and Epstein–Barr virus, and Candida albicans infections. HNSCC has causative links to both environmental factors and genetic mutations, with the latter playing a more critical role in cancer progression. These molecular changes to epithelial cells include the inactivation of cancer suppressor genes and proto-oncogenes overexpression, resulting in tumour cell proliferation and distant metastasis. HNSCC patients have impaired dendritic cell (DC) and natural killer (NK) cell functions, increased production of higher immune-suppressive molecules, loss of regulatory T cells and co-stimulatory molecules and major histocompatibility complex (MHC) class Ι molecules, lower number of lymphocyte subsets, and a poor response to antigen-presenting cells. At present, the standard treatment modalities for HNSCC patients include surgery, chemotherapy and radiotherapy, and combinatorial therapy. Despite advances in the development of novel treatment modalities over the last few decades, survival rates of HNSCC patients have not increased. To establish effective immunotherapies, a greater understanding of interactions between the immune system and HNSCC is required, and there is a particular need to develop novel therapeutic options. A therapeutic cancer vaccine has been proposed as a promising method to improve outcome by inducing a powerful adaptive immune response that leads to cancer cell elimination. Compared with other vaccines, peptide cancer vaccines are more robust and specific. In the past few years, there have been remarkable achievements in peptide-based vaccines for HNSCC patients. Here, we summarize the latest molecular alterations in HNSCC, explore the immune response to HNSCC, and discuss the latest developments in peptide-based cancer vaccine strategies. This review highlights areas for valuable future research focusing on peptide-based cancer vaccines.

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“…Sensitivity testing of novel immunotherapeutic approaches is impaired as they require an intact immune system to be effective. Results from co-culture studies ( Sawant et al, 2016 ) give clear evidence that the TME exerts tumor-promoting effects ( Curry et al, 2014 ) which is a strong argument for the establishment and implementation of more advanced 3D tumor models ( Tinhofer et al, 2020 ). Cancer-associated fibroblasts (CAFs), one of the major components in TME, play a critical role in tumorigenesis.…”

Section: Preclinical Tumor Models For Hnsccmentioning

confidence: 99%

Precision Medicine Gains Momentum: Novel 3D Models and Stem Cell-Based Approaches in Head and Neck Cancer

Affolter

Lammert

Kern

et al. 2021

Front. Cell Dev. Biol.

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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.

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Preclinical models of head and neck squamous cell carcinoma for a basic understanding of cancer biology and its translation into efficient therapies

Cited by 29 publications

References 70 publications

Patient-Derived Organoids as a Model for Cancer Drug Discovery

Patient-Derived Organoids as a Model for Cancer Drug Discovery

Head and Neck Squamous Cell Carcinoma: Risk Factors, Molecular Alterations, Immunology and Peptide Vaccines

Precision Medicine Gains Momentum: Novel 3D Models and Stem Cell-Based Approaches in Head and Neck Cancer

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