Hypopharyngeal cancer has one of the highest mortality rates of any of the head and neck cancers, with a 5-year survival rate of only 32%. The treatments currently available are severely lacking and, due to the heterogeneity of the disease, the right treatments for individual patients are difficult to identify. The research proposed here will take an important step toward matching hypopharyngeal cancer patients with therapeutics that can benefit them. Proteins are the drivers of biology and disease, and recent technological advancements allow us to measure thousands of proteins simultaneously. We will use these technological advances to investigate hypopharyngeal cancer patient samples to define the biology driving the cancer more accurately across different patients.

The Focus Areas addressed with this research are:

Focus Area 1 – Biology and Etiology: Identify disease-defining molecular pathways, cell context, and microenvironment.

Focus Area 2 – Research Model: Develop and validate rare tumor-specific models that can support clinical trial.

Focus Area 3 – Therapy: Identify novel therapeutic strategies, including drug repurposing.

Hypopharyngeal cancers initiate in the hypopharynx at the bottom of the throat, and as with other head and neck cancers, the overwhelming majority (95%) are squamous cell carcinomas (SCCs). Squamous cells of the throat are directly exposed to what we consume and detrimental habits such as smoking, chewing tobacco, heavy alcohol use, and poor diet, are significantly correlated with the development of hypopharyngeal cancer. According to the National Institute on Drug Abuse, military deployment, and its concomitant stresses, are associated with smoking initiation and unhealthy drinking. Therefore, deployed Servicemen and Veterans are more vulnerable to these cancers given the higher rate of alcohol and substance abuse linked to those with Post Traumatic Stress Disorder (PTSD). Hypopharyngeal cancer is a heterogeneous disease, and a key aspect to matching patients to therapeutics and developing novel therapeutics is functional predictive model systems that represent clinical patients. We will develop those models and do early screening on Food and Drug Administration-approved drugs to identify novel therapeutics that could be used in the clinic. The immediate impact will be improved stratification of hypopharyngeal cancer patients that will help drive therapeutic decisions in the clinic. The long-term impact is the development of predictive model systems that can be used to develop novel drugs targeted to particular patient subsets where they will be efficacious. Rare cancers are often underrepresented in the research community, and this will be a significant step for hypopharyngeal cancer and a proof of concept that can be applied to other rare cancers.