Date of Award

12-1-2015

Degree Name

Doctor of Philosophy

Department

Molecular Biology, Microbiology and Biochemistry

First Advisor

Rao, Krishna

Abstract

Platinum-based therapy is the most often used chemotherapeutic agent to treat advanced cases of head and neck cancers. However, only a small fraction of the patient population responds to cisplatin, with a median survival time of less than a year. Currently, there is a lack of clinically employable molecular characterization of the disease beyond HPV status to classify patients who would respond favorably to platinum-based therapy. In this regard, CD24 expression level appears to be a significant molecular phenotype of cisplatin resistance in laryngeal carcinoma. This study demonstrates that CD24 expression level in HNSCC has a linear relationship with cisplatin resistance, and it affects the transcription of critical apoptotic, stem, and drug resistance genes. The knockdown of the CD24 transcript reduces tumor growth rate and increases the overall cisplatin sensitivity in mice xenograft experiments. A retrospective analysis of a cohort of 25 HNSCC patient tumor samples suggests that CD24-high tumors go on to show an unfavorable response to cisplatin treatment. Overall, based on the strength of further clinical analysis, CD24 presents a strong rationale to be utilized as a predictive indicator to stratify head and neck cancer patients for platinum-based therapy. This study also provides a rationale for using CD24 as a therapeutic adjuvant target along with standard cisplatin therapy in head and neck cancers.

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