PMID- 38201496
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240114
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 16
IP  - 1
DP  - 2023 Dec 22
TI  - A New Hypothesis Describing the Pathogenesis of Oral Mucosal Injury Associated 
      with the Mammalian Target of Rapamycin (mTOR) Inhibitors.
LID - 10.3390/cancers16010068 [doi]
LID - 68
AB  - It has been 24 years since rapamycin (sirolimus) was approved to mitigate solid 
      organ transplant rejection and 16 years since mTOR (mammalian/mechanistic target 
      of rapamycin) inhibitors reached patients as a cancer therapy. While the clinical 
      benefits of mTOR inhibitors (mTORi) are robust, so too are their toxicities. 
      Among the most common issues is the development of ulcers of the oral mucosa 
      (mTOR-inhibitor associated stomatitis; mIAS). These lesions are distinct from 
      those of other anti-cancer agents, occur with regularity, and impact patient 
      outcomes. mIAS' pathogenesis has been the subject of speculation, and its similar 
      presentation to recurrent aphthous stomatitis (RAS) has led to the hypothesis 
      that it might serve as a surrogate to better understand RAS. Based on a review of 
      the literature, the current manuscript provides a hypothesis regarding the 
      mechanisms by which mTORis uniquely initiate mucosal injury and an explanation 
      for the observation that steroids (also an immunosuppressive) are effective in 
      its treatment through a non-immunologic mechanism. Unexplained unique features of 
      mIAS are discussed in this review in the context of future investigation.
FAU - Sonis, Stephen T
AU  - Sonis ST
AD  - Divisions of Oral Medicine and Dentistry, Brigham and Women's Hospital and the 
      Dana-Farber Cancer Institute, Boston, MA 02115, USA.
AD  - Department of Oral Medicine, Infection and Immunity, Harvard School of Dental 
      Medicine, Boston, MA 02114, USA.
AD  - Biomodels, LLC, Waltham, MA 02451, USA.
FAU - Villa, Alessandro
AU  - Villa A
AUID- ORCID: 0000-0002-1966-6000
AD  - Oral Medicine, Oral Oncology and Dentistry, Miami Cancer Institute, Miami, FL 
      33176, USA.
AD  - Herbert Wertheim College of Medicine, Florida International University, Miami, FL 
      33199, USA.
LA  - eng
PT  - Journal Article
DEP - 20231222
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC10777973
OTO - NOTNLM
OT  - aphthous
OT  - cancer
OT  - everolimus
OT  - mTOR inhibitor
OT  - oral ulceration
OT  - rapamycin
COIS- Sonis is an employee of Biomodels, LLC and Primary Endpoint Solutions, LLC. Both 
      companies assist industry, government and academics to study and enable drugs, 
      biologicals and devices to treat patients with a variety of indications, 
      including cancer and the side effects and toxicities of its treatment. Sonis does 
      not have interests in any of the companies with which either organization works. 
      Alessandro Villa is a consultant for Primary Endpoint Solutions, LLC.
EDAT- 2024/01/11 07:43
MHDA- 2024/01/11 07:44
PMCR- 2023/12/22
CRDT- 2024/01/11 01:06
PHST- 2023/11/27 00:00 [received]
PHST- 2023/12/13 00:00 [revised]
PHST- 2023/12/15 00:00 [accepted]
PHST- 2024/01/11 07:44 [medline]
PHST- 2024/01/11 07:43 [pubmed]
PHST- 2024/01/11 01:06 [entrez]
PHST- 2023/12/22 00:00 [pmc-release]
AID - cancers16010068 [pii]
AID - cancers-16-00068 [pii]
AID - 10.3390/cancers16010068 [doi]
PST - epublish
SO  - Cancers (Basel). 2023 Dec 22;16(1):68. doi: 10.3390/cancers16010068.