دورية أكاديمية
أعرض في EDS

Assessment of Mammalian Target of Rapamycin Pathway Activation in Basal Cell Carcinoma as a New Therapeutic Approach.

التفاصيل البيبلوغرافية
العنوان: Assessment of Mammalian Target of Rapamycin Pathway Activation in Basal Cell Carcinoma as a New Therapeutic Approach.
المؤلفون: Chang ALS; Department of Dermatology, Stanford University School of Medicine, Redwood City, CA., Brown R; Department of Dermatology, Stanford University School of Medicine, Redwood City, CA.; Department of Pathology, Stanford University School of Medicine, Palo Alto, CA; and., Li S; Departments of Dermatology and Urology, Stanford University School of Medicine, Redwood City, CA., Betancourt N; Department of Dermatology, Stanford University School of Medicine, Redwood City, CA., Teng J; Department of Dermatology, Stanford University School of Medicine, Redwood City, CA.
المصدر: The American Journal of dermatopathology [Am J Dermatopathol] 2024 Sep 01; Vol. 46 (9), pp. 588-592. Date of Electronic Publication: 2024 Apr 23.
نوع المنشور: Journal Article; Case Reports
اللغة: English
بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 7911005 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1533-0311 (Electronic) Linking ISSN: 01931091 NLM ISO Abbreviation: Am J Dermatopathol Subsets: MEDLINE
أسماء مطبوعة: Publication: Hagerstown, MD : Lippincott Williams & Wilkins
Original Publication: New York, Masson Publishing USA.
مواضيع طبية MeSH: Skin Neoplasms*/drug therapy , Skin Neoplasms*/pathology , Skin Neoplasms*/metabolism , Carcinoma, Basal Cell*/drug therapy , Carcinoma, Basal Cell*/pathology , Carcinoma, Basal Cell*/metabolism , TOR Serine-Threonine Kinases*/metabolism , TOR Serine-Threonine Kinases*/antagonists & inhibitors , Sirolimus*/pharmacology , Sirolimus*/therapeutic use , Signal Transduction*/drug effects , MTOR Inhibitors*/pharmacology , MTOR Inhibitors*/therapeutic use, Humans ; Male ; Female ; Middle Aged ; Adult ; Aged ; Basal Cell Nevus Syndrome/drug therapy ; Basal Cell Nevus Syndrome/pathology ; Basal Cell Nevus Syndrome/metabolism ; Immunohistochemistry ; Antibiotics, Antineoplastic ; Child ; Adolescent ; Young Adult ; Aged, 80 and over ; Proto-Oncogene Proteins c-akt/metabolism ; Off-Label Use ; Treatment Outcome ; Cell Cycle Proteins ; Adaptor Proteins, Signal Transducing
مستخلص: Abstract: Targeting the mammalian target of rapamycin (mTOR) pathway represents a potentially novel approach to treat basal cell carcinoma (BCC), but activation of this pathway has not been well described in human BCCs. The purpose of this study was to assess whether mTOR pathway activation occurs in BCCs (both sporadic and syndromic) and report a case of a patient with Gorlin syndrome (GS) whose clinically suspicious BCCs responded to mTOR inhibition through topical sirolimus treatment. After Stanford Institutional Review Board Approval, archived BCCs from patients with GS (n = 25), sporadic BCCs (n = 35), and control tissues were subjected to immunohistochemical analysis for the activation of mTOR pathway, and immunohistochemical staining intensity was evaluated by a dermatopathologist. BCCs (compared with normal skin) had elevated levels of eIF4EBP1 ( Padjusted = 0.0336), which is downstream of mTOR. a serine/threonine kinase Phospho-(AKT), which interacts with mTOR, was also significantly elevated (perinuclear: Padjusted < 0.0001; cytoplasmic: Padjusted = 0.0021). When off-label topical 1% sirolimus was used on a pediatric patient with GS, we noted reduction of new BCC development and decreased size of existing neoplasms clinically suspicious for BCCs. This treatment was well tolerated after 2 years of continuous use, with no other treatments needed during this period. Topical sirolimus is a promising therapeutic candidate against both sporadic and GS-associated BCC. Multicenter, prospective studies are needed to understand the efficacy and safety of topical mTOR inhibitors in BCC treatment, and ascertain whether the immunohistochemical markers downstream of mTOR could have predictive value in identifying BCCs most likely to respond to topical mTOR inhibitors, such as sirolimus.
(Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
References: Cancer Cell. 2015 Mar 9;27(3):342-53. (PMID: 25759020)
Orphanet J Rare Dis. 2016 Sep 01;11(1):120. (PMID: 27581207)
Exp Dermatol. 2021 Mar;30(3):358-366. (PMID: 33617094)
J Invest Dermatol. 2018 Aug;138(8):1716-1725. (PMID: 29550418)
N Engl J Med. 2012 Jun 7;366(23):2171-9. (PMID: 22670903)
Curr Med Chem. 2022;29(20):3501-3529. (PMID: 35209811)
Oncotarget. 2019 Feb 15;10(14):1360-1387. (PMID: 30858923)
Lancet Oncol. 2015 Jun;16(6):716-28. (PMID: 25981810)
J Am Acad Dermatol. 2022 Nov;87(5):1163-1166. (PMID: 35219749)
JAMA Dermatol. 2013 May;149(5):639-41. (PMID: 23677114)
JAMA Dermatol. 2014 Aug;150(8):877-9. (PMID: 24898076)
المشرفين على المادة: EC 2.7.11.1 (TOR Serine-Threonine Kinases)
W36ZG6FT64 (Sirolimus)
EC 2.7.1.1 (MTOR protein, human)
0 (MTOR Inhibitors)
0 (Antibiotics, Antineoplastic)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
0 (EIF4EBP1 protein, human)
0 (Cell Cycle Proteins)
0 (Adaptor Proteins, Signal Transducing)
تواريخ الأحداث: Date Created: 20240422 Date Completed: 20240816 Latest Revision: 20240818
رمز التحديث: 20240818
مُعرف محوري في PubMed: PMC11328919
DOI: 10.1097/DAD.0000000000002718
PMID: 38648034
قاعدة البيانات: MEDLINE
الوصف
تدمد:1533-0311
DOI:10.1097/DAD.0000000000002718