Elizabeth J. Franzmann, M.D.
Associate Professor of Otolaryngology
Description of Research
Dr. Franzmann’s major research interests include: molecular mechanisms of head and neck cancer progression; head and neck cancer early detection in diverse populations; and therapeutic targets in head and neck cancer.
The lab is interested in the molecular mechanisms of head and neck squamous cell cancer (HNSCC) progression. Despite rigorous therapy using various combinations of surgery, radiation and chemotherapy initial treatment of HNSCC is successful only 50% of the time. Because of the complexity of the head and neck, current therapy often results in facial disfigurement, speech and swallowing problems and substantial healthcare costs. Certain groups including blacks and the economically disadvantaged suffer disproportionately from this disease. Improved screening and staging methods for HNSCC are needed.
Dr. Franzmann’s lab is investigating a simple, inexpensive early detection method for HNSCC. Many millions are threatened by this disease since the main risk factors are tobacco and alcohol use and the Human Papillomavirus (HPV). Data on over 180 subjects suggests that the soluble form of CD44, an adhesion molecule involved in tumorigenesis, is elevated in oral rinses of HNSCC patients compared to controls, distinguishing HNSCC from those without disease with 62-79% sensitivity and 88-100% specificity (CEBP 2007). Subsequent work suggests that another marker also found in oral rinses, total protein, along with certain demographic and risk variables further improves results (AUC=0.85)(Head Neck 2012, Cancer Biomarkers 2012). The test is now patented and licensed to Vigilant Biosciences. Since the test uses oral rinses and simple ELISA or ELISA-like assays, it is very easy to administer, noninvasive and inexpensive. Such qualities are very important for populations with limited access to expert care. Our most recent work, suggests that this diagnostic is particularly effective in an African Americans.
The lab is also investigating CD44 as a target for therapy. This target is exciting because it is overexpressed in HNSCC, associated with a poor prognosis, and present on HNSCC cancer stem cells. Our recent work with HNSCC xenografts shows that knockdown of CD44 results in decreased tumor growth, reduced CD44 expression and down regulation of EGFR and a phosphorylated form of EGFR (Oral Oncology, 2012). The CD44 family consists of multiple isoforms. One of these, CD44v3, is known to have a growth factor binding site. Dr Franzmann’s group has shown that CD44v3 is overexpressed in HNSCC compared to normal tissue and is also an interesting target for therapy.
- Determined that solCD44 and total protein levels are elevated in HNSCC cases compared to controls and the combination may be useful for detecting HNSCC, especially in the African-American population.
- Dr. Franzmann is Inventor on US Patent number 8088591. Issued Jan 3, 2012. Biomarkers for detection and diagnosis of head and neck squamous cell carcinoma. Licensed to Vigilant Biosciences. Two related IP items are pending.
- CD44 overexpression results in increased HNSCC cell proliferation, migration and cisplatin resistance, while knock-down results in decreased tumor growth in nude mice.
- A Roche monoclonal antibody against CD44 effective decreased HNSCC xenograft growth in nude mice and expression of CD44, EGFR and phosphorylated EGFR. The drug also appears to increase cetuximab-mediated ADCC.
- Dr. Franzmann is one of the Inventors on pending patent with Roche to use a monoclonal antibody against CD44 (already in Phase I testing) for the specific indication of head and neck cancer.
- Shown that CD44v3, an alternatively spliced isoform of CD44 that contains a growth factor binding domain, is overexpressed at the transcript level in HNSCC tissues compared to control tissues. Overexpression of the CD44v3 isoform in a HNSCC cell lines is associated with increased cell migration.
- Germani RM, Civantos FJ, Elgart G, Roberts B, Franzmann EJ. Molecular markers of micrometastasis in oral cavity carcinomas. Otolaryngol Head Neck Surg 141:52-8, 2009. Read more »