IL-6 blockade in head and neck cancer.

In silico models accurately predict in vivo response for IL-6 blockade in head and neck cancer.:

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In silico models accurately predict in vivo response for IL-6 blockade in head and neck cancer.

Cancer Res. 2020 Feb 10;:

Authors: Nazari F, Oklejas AE, Nör JE, Pearson AT, Jackson TL

Abstract

Malignant features of head and neck squamous cell carcinoma (HNSCC) may be derived from the presence of stem-like cells that are characterized by uniquely high tumorigenic potential. These cancer stem cells (CSCs) function as putative drivers of tumor initiation, therapeutic evasion, metastasis, and recurrence. Though they are an appealing conceptual target, CSC-directed cancer therapies remain scarce. One promising CSC target is the interleukin-6 (IL-6) pathway, which is strongly correlated with poor patient survival. In this study we created and validated a multiscale mathematical model to investigate the impact of crosstalk between tumor cell (TC)- and endothelial cell (EC)- secreted IL-6 on HNSCC growth and the CSC fraction. We then predicted and analyzed the responses of HNSCC to tocilizumab (TCZ) and cisplatin combination therapy. The model was validated with in vivo experiments involving human ECs co-implanted with HNSCC cell line xenografts. Without artificial tuning to the laboratory data, the model showed excellent predictive agreement with the decrease in tumor volumes observed in TCZ treated mice, as well as a decrease in the CSC fraction. This computational platform provides a framework for preclinical cisplatin and tocilizumab dose and frequency evaluation to be tested in future clinical studies.

PMID: 32041834 [PubMed - as supplied by publisher]