Discovery of Oral Cancer Target May Lead to New Treatments

Researchers at Boston University School of Medicine (BUSM) have identified a marker that can detect carcinoma-associated fibroblasts (CAFS) in oral cancer tissues. This marker, platelet-derived growth factor receptor-beta (PDGFRβ), may lead to a new treatment that could work with existing treatments to provide a more effective cancer therapy.

CAFs are strong predictors of disease severity, but isolating tissue samples and identifying reliable markers is challenging.

The findings, first published in PLOS ONE, demonstrate how the researchers are combining bioinformatics analysis of gathered gene expression datasets, along with experimental assays using oral cancer specimens and cell lines.

The researchers identified a set of collagen genes they hypothesized to be mostly CAF-specific: COL1A1, COL1A2 and COL3A1. Using a large gene expression dataset from the cancer genome atlas comprising hundreds of oral cancer samples, the team looked for more genes whose expression best associated with the average expression of these three collagen genes. In doing so, they were able to identify several markers, including PDGFRβ, which was confirmed to be CAF-specific. This confirmation was done using immunostaining assays in oral carcinoma specimens.

“Given the known association of CAFs with poor prognosis in certain cancers, including those of the head and neck, the identification of robust and reliable markers of these cells is necessary to further assess their role in tumor initiation and progression,” explained Maria Trojanowska, PhD, professor of medicine at BUSM, in a news release.

Also known as head and neck cancers, oral cancers arise from a variety of causes, including alcohol and tobacco use and being infected with human papilloma virus (HPV), which is transmissible through oral- sexual contact. There has been an uptick in the HPV infection in recent years.

Approximately 48,330 people will be diagnosed with oral cavity or oropharyngeal cancer this year, according to the American Cancer Society. An estimated 9,570 people will die of these cancers annually. These cancers, when caught early, are treatable, but are often discovered in later stages because of the difficulty of diagnosing them.