Abstract
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.
Highlights
The pathogenesis and clinical phenotype of oral mucositis caused by high-dose chemotherapy or radiotherapy are well described in the literature [1,2,3,4,5,6,7,8]
This review summarizes the state-of-the-science regarding the pathobiology, clinical characteristics, and management of mTORI-associated stomatitis (mIAS), and delineates new research directions with an emphasis on the pathogenesis of oral mucosal pain
Despite the clinical importance of pain from cancer therapy-induced oral mucosal injury, its etiology and pathobiology have not been well defined in the setting of mammalian target of rapamycin (mTOR) inhibitors because of difficulty in generating preclinical models that replicate oral ulceration and pain in patients receiving these targeted therapeutics
Summary
The pathogenesis and clinical phenotype of oral mucositis caused by high-dose chemotherapy or radiotherapy are well described in the literature [1,2,3,4,5,6,7,8]. Insights into the mechanism of action of mTOR inhibitors and naturally occurring oral mucosal lesions such as recurrent aphthous ulceration may be valuable in informing future research directions involving mIAS. The collective evidence involving the mechanisms of mTOR inhibitors and the lessons learned at the clinical and research levels for recurrent aphthous ulceration may provide important context for new research directed to mIAS pathobiology This new knowledge could over time lead to an enhanced ability of the clinician to predict risk for development of mIAS and predict the response to therapeutic intervention on an individual patient-by-patient approach. Despite the clinical importance of pain from cancer therapy-induced oral mucosal injury, its etiology and pathobiology have not been well defined in the setting of mTOR inhibitors because of difficulty in generating preclinical models that replicate oral ulceration and pain in patients receiving these targeted therapeutics. Assessment of other possible oral morbidities Evaluate for herpetic, bacterial, and fungal infections Administer antimicrobials as appropriate
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