Head and neck cancers (HNC), like most solid tumours, contain a subpopulation of cancer stem cells (CSC) that are commonly responsible for treatment failure. Conventional therapies are unsuccessful in controlling CSCs, thus novel, targeting therapies are needed. A promising agent is ATRA (All-trans-retinoic acid) that was shown to induce CSC differentiation, cell cycle redistribution and CSCs radiosensitisation. To add to the limited data, this work simulated the effects of ATRA on a virtual HNC and evaluated tumour response to radiotherapy. A Monte Carlo technique was employed to grow a HNC consisting of all lineages of cancer cells. The biologically realistic input parameters led to a pre-treatment CSC population of 5.9%. The Linear Quadratic model was employed to simulate radiotherapy. ATRA-induced differentiation, cell arrest and apoptosis were modelled, based on literature data. While the effect of differentiation was marginal, the strongest influence on CSC subpopulation was displayed by ATRA’s cell arrest effect via an exponential behaviour of the dose-response curve. The apoptotic effect induced by ATRA shows linear correlation between the percentage of apoptotic cells and dose required to eradicate CSCs. In conclusion, ATRA is a potent CSC-targeting agent with viable impact on tumour control when combined with radiotherapy.
Chemoradiotherapy remains the most common management of locally advanced head and neck cancer. While both treatment components have greatly developed over the years, the quality of life and long-term survival of patients undergoing treatment for head and neck malignancies are still poor. Research in head and neck oncology is equally focused on the improvement of tumour response to treatment and on the limitation of normal tissue toxicity. In this regard, personalised therapy through a multi-omics approach targeting patient management from diagnosis to treatment shows promising results. The aim of this paper is to discuss the latest results regarding the personalised approach to chemoradiotherapy of head and neck cancer by gathering the findings of the newest omics, involving radiotherapy (dosiomics), chemotherapy (pharmacomics), and medical imaging for treatment monitoring (radiomics). The incorporation of these omics into head and neck cancer management offers multiple viewpoints to treatment that represent the foundation of personalised therapy.
Growth kinetics strongly influence tumour responses to treatment. Slowly growing tumours showed linear dependence between dose and hypoxia/CSC, whereas rapidly growing tumours followed exponential behaviour.
The model shows that ATRA exhibits a powerful effect on CSCs when combined with radiotherapy. However, the more radioresistant quiescent cell population should not be ignored, as it can be a potential threat to treatment outcome when cells are recruited into the cell cycle.
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