Comprehensive portrait of FGFR expression in circulating tumor cells of head and neck cancer

Abstract

Head and neck cancer represents 600,000 new cancers worldwide each year, and almost 90% of them are squamous cell carcinoma (HNSCC). With the exception of HPV status with its known implications, numerous molecular and clinical risk factors have been investigated over the decades. Unfortunately, these risk factors have demonstrated limited clinical utility, and prognostic biomarker research has not provided clinically relevant markers that have the capability of predicting response to therapies that target specific oncogenic pathways. In view of the relationship shown by several studies of FGFR and other signaling pathways, it is critically important to search for molecular assays that have the capability to predict patient response to anti-FGFR therapy in HNSCC. Circulating tumor cells (CTCs) are extraordinarily rare cells that circulate in the blood of patients with cancer and have been show to reflect changes in the patient's primary tumor. Dynamic changes within this rare cell population may be a less invasive means to analyze tumor changes associated with FGF/FGFR signaling in response to anti-FGFR therapy and may give important insights on how FGFR may contribute to metastasis. Here, we aim to combine the unique ability of the CTC-iChip to isolated these CTCs in an antigen-independent manner with molecular analysis tools to the explore the role of FGFR in CTCs derived from HNSCC patients. We also aim to establish an imaging strategy for precise, automated quantification and molecular characterization of FGFR expression in CTCs, along with nucleic acid analysis of FGFR transcripts. This study will comprise head and neck squamous cell carcinoma patients being treated at the Massachusetts General Hospital. Protein expression of members of the FGFR family will be assessed by immunofluorescence assays and automated multispectral imaging. FGFR transcripts will be analyzed using microfluidic digital qRT-PCR. Data will be reported as mean standard error of the mean as noted. If groups had a normal distribution and homogeneous variances, the group means were compared by an independent t-test. Differences were considered significant at the 95% confidence level (p < 0.05). (AU)