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Oral mucosal injury caused by mammalian target of rapamycin inhibitors: emerging perspectives on pathobiology and impact on clinical practice.

  • Peterson, Douglas E1
  • O'Shaughnessy, Joyce A2
  • Rugo, Hope S3
  • Elad, Sharon4, 5
  • Schubert, Mark M6
  • Viet, Chi T7
  • Campbell-Baird, Cynthia8
  • Hronek, Jan9
  • Seery, Virginia10
  • Divers, Josephine2
  • Glaspy, John11
  • Schmidt, Brian L7
  • Meiller, Timothy F12
  • 1 School of Dental Medicine and Neag Comprehensive Cancer Center, UConn Health, Farmington, Connecticut.
  • 2 Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, Texas.
  • 3 UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
  • 4 Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, New York.
  • 5 Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York.
  • 6 School of Dentistry, University of Washington and Seattle Cancer Care Alliance, Seattle, Washington.
  • 7 New York University College of Dentistry, New York, New York.
  • 8 Penn State Hershey Medical Center, Hershey, Pennsylvania.
  • 9 Tennessee Oncology/Sarah Cannon Research Institute, Nashville, Tennessee.
  • 10 Beth Israel Deaconess Medical Center, Boston, Massachusetts. , (Israel)
  • 11 Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California.
  • 12 School of Dentistry and the Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland.
Published Article
Cancer Medicine
Publication Date
Aug 01, 2016
DOI: 10.1002/cam4.761
PMID: 27334013


In recent years oral mucosal injury has been increasingly recognized as an important toxicity associated with mammalian target of rapamycin (mTOR) inhibitors, including in patients with breast cancer who are receiving everolimus. This review addresses the state-of-the-science regarding mTOR inhibitor-associated stomatitis (mIAS), and delineates its clinical characteristics and management. Given the clinically impactful pain associated with mIAS, this review also specifically highlights new research focusing on the study of the molecular basis of pain. The incidence of mIAS varies widely (2-78%). As reported across multiple mTOR inhibitor clinical trials, grade 3/4 toxicity occurs in up to 9% of patients. Managing mTOR-associated oral lesions with topical oral, intralesional, and/or systemic steroids can be beneficial, in contrast to the lack of evidence supporting steroid treatment of oral mucositis caused by high-dose chemotherapy or radiation. However, steroid management is not uniformly efficacious in all patients receiving mTOR inhibitors. Furthermore, technology does not presently exist to permit clinicians to predict a priori which of their patients will develop these lesions. There thus remains a strategic need to define the pathobiology of mIAS, the molecular basis of pain, and risk prediction relative to development of the clinical lesion. This knowledge could lead to novel future interventions designed to more effectively prevent mIAS and improve pain management if clinically significant mIAS lesions develop. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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