DF/HCC Program Affiliation

Head and Neck Cancer

Research Abstract

The mouth is a common site for both acute and long term toxicities associated with antineoplastic drug and radiation therapy. Ulcerative mucositis is a common, bothersome, dose-limiting toxicity of both radiation- and chemotherapy. In addition, among myelosuppressed patients, breaks in the oral mucosa caused by mucositis provide a robust portal of entry for oral microorganisms and result in the mouth being the most common identifiable site of bacteremias in this patient population. The oral mucosa is a frequent target tissue of graft-vs-host disease. The lesions that result are often functionally debilitating. The objective of our research is to better understand the pathobiology of these conditions and to investigate new forms of intervention which are mechanistically based. To accomplish this objective, our laboratory has employed innovative animal models for both chemotherapy- and radiation-induced mucositis. Murine models for gvhd are also used. Among the techniques which are used are immunohistochemistry, electron microscopy, PCR, and assays to assess cell proliferation. Bisphosphonates have been associated with osteonecrosis of the jaws. Using a newly developed animal model, we are actively defining the biological events the lead to the condition and correlate with clinical and imaging outcomes. Clinical studies include Phase I, II and III protocols for new therapies to treat or prevent mucosal injuries, development and assessment of outcome measures for stomatotoxicities, and pharmacoeconomic analyses of oral complications of cancer therapies. Since mucositis affects all areas of the GI tract, models to study mechanism and interventions are also being studied for radiation-induced esophagitis, colitis, and proctitis.

Publications

• Sonis S, Haddad R, Posner M, Watkins B, Fey E, Morgan TV, Mookanamparambil L, Ramoni M.Gene expression changes in peripheral blood cells provide insight into the biological mechanisms associated with regimen-related toxicities in patients being treated fo
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• Vera-Llonch M, Oster G, Hagiwara M, Sonis S.Oral mucositis in patients undergoing radiation treatment for head and neck carcinoma.Cancer 2006 Jan 15;106(2):329-36.
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• Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, Bekele BN, Raber-Durlacher J, Donnelly JP, Rubenstein EB, ,.Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patien
  15108222
• Sonis ST.The pathobiology of mucositis.Nat Rev Cancer 2004 Apr;4(4):277-84.
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• Loury D, Embree JR, Steinberg DA, Sonis ST, Fiddes JC.Effect of local application of the antimicrobial peptide IB-367 on the incidence and severity of oral mucositis in hamsters.Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999 May;87(5):544-51.
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• Sonis ST, Eilers JP, Epstein JB, LeVeque FG, Liggett WH, Mulagha MT, Peterson DE, Rose AH, Schubert MM, Spijkervet FK, Wittes JP.Validation of a new scoring system for the assessment of clinical trial research of oral mucositis induced by radiation or che
  10326686