Mathematical Model for IL-6-Mediated Tumor Growth, and Targeted Treatment

Head and neck squamous cell carcinoma (HNSCC), the sixth most common cancer

type worldwide, accounts for more than 630,000 new cases and 350,000 deaths

annually. Drug-resistance and tumor recurrence are the most challenging problems

in head and neck cancer treatment. It is hypothesized that a very small fraction

of stem-like cells within HNSCC tumor, called cancer stem cells (CSCs), is

responsible for tumor initiation, progression, resistance and recurrence. It has also

been shown that IL-6 secreted by head and neck tumor-associated endothelial cells

(ECs) enhances the survival, self-renewal and tumorigenic potential of head and

neck CSCs. In this study we will use a mathematical multi-scale model which operates

at the intracellular, molecular, and tissue level to investigate the impacts of

EC-secreted IL-6 signaling on the crosstalk between tumor cells and ECs during

tumor growth. This model will be calibrated by using the experimental in vivo

data.

Eventually the model will be modified to explore the responses of head and neck

cancer cells to combination therapy involving Tocilizumab (an anti-IL-6R antibody)

and Cisplatin (the most frequently used chemotherapy for head and neck

cancer). The model will be able to predict the final proportion of CSCs in response

to endothelial cell-secreted IL-6 and drug therapies. The model will be validated

by directly comparing the experimental treatment data and the model predictions.

This could potentially provide a condition under which we could control enlargement

of the head and neck CSC pool and tumor recurrence. It may also suggest

the best bounds for Cisplatin and/or Tocilizumab dose and frequency to be tested

in the clinical trial.