Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with a 50% rate of local failure with current standard of care. We recently reported that patient-derived tumor associated fibroblasts (TAF) facilitate HNSCC proliferation and metastasis to the cervical lymph node and lung of mice. Although the paracrine molecular interactions between HNSCC and TAFs have not been fully described, we demonstrated that TAFs (and not HNSCC) secrete hepatocyte growth factor (HGF), a ligand for the c-Met receptor on HNSCC cells. Further, activation of the HGF-c-Met pathway increased HNSCC growth and invasion. In addition, we demonstrated that HNSCC cells induce the expression of HGF from TAFs. We hypothesized that inhibition of TAF-secreted HGF would reduce HNSCC proliferation, invasion and migration. We tested the efficacy of ficlatuzumab (AV-299) a humanized HGF inhibitory immunoglobulin G1 (IgG1) monoclonal antibody in mitigating TAF-induced HNSCC progression. . Ficlatuzumab exhibits antitumor effects in xenograft models as a single agent and has been tested in patients with non-small cell lung cancer in a phase I setting. The antitumor efficacy of HGF neutralization has not been tested in the context of TAFs in HNSCC. Our data demonstrate that ficlatuzumab is effective in mitigating TAF-induced HNSCC proliferation, migration and invasion through inhibition of the c-met pathway in HNSCC.
Citation Format: Chase Hamilton, Shary Shelton, Kiran Kakarala, Sufi Mary Thomas. Tumor-associated fibroblasts: A new target for cancer treatment. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A55. doi:10.1158/1538-7445.CHTME14-A55