Cancer stem cells are thought to be responsible for the heartiness of skin cancer on the head and neck. One student's math model predicts how these cancer stem cells would react to combination therapy, and may help determine the ideal treatment application.
Fereshteh Nazari, an applied mathematics doctoral candidate in the School of Human Evolution and Social Change, will defend her dissertation, "Mathematical Model for IL-6-Mediated Tumor Growth, Invasion and Targeted Treatment." Her committee members are Professor Carlos Castillo-Chavez (co-chair), Professor Trachette Jackson (co-chair), and Professor Sherry Towers.
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 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 is calibrated by using experimental in vivo data. The preliminary model of cancer stem cell driven tumor growth is then 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 is able to predict the final proportion of CSCs in response to endothelial cell-secreted IL-6, as well as to cytotoxic and targeted drug therapies. The model is validated by directly comparing the experimental treatment data and the model predictions. Continued modeling in this direction could potentially uncover the conditions for which the enlargement of the head and neck CSC pool and tumor recurrence can be controlled. It may also suggest the best bounds for Cisplatin and/or Tocilizumab dose and frequency to be tested in clinical trials.