Drugs targeting epithelial-mesenchymal transition molecules for treatment of lichen planopilaris.

Publisher: Oxford University Press Country of Publication: England NLM ID: 7606847 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2230 (Electronic) Linking ISSN: 03076938 NLM ISO Abbreviation: Clin Exp Dermatol Subsets: MEDLINE

Publication: 2023- : Oxford : Oxford University Press
Original Publication: Oxford : Blackwell Scientific Publications.

Epithelial-Mesenchymal Transition* ; Lichen Planus*/drug therapy ; Lichen Planus*/pathology; Alopecia/pathology ; Cicatrix/pathology ; Humans ; Skin/pathology

Primary cicatricial alopecia (PCA), also known as scarring alopecia, comprises a diverse group of hair disorders that cause permanent destruction of the pilosebaceous unit, resulting in disappearance of the follicular ostia. Lichen planopilaris (LPP) is a subtype of primary lymphocytic cicatricial alopecia. There is an urgent need to identify novel molecules that successfully target specific pathogenic pathways in LPP to inhibit and reverse disease progression. Recent studies into LPP pathogenesis have discovered that follicular stem cells undergo epithelial-mesenchymal transition (EMT). We sought to identify drugs that target molecules involved in EMT to repurpose these drugs for treatment of LPP. We identified 8 molecules and 15 drugs that target these EMT molecules. Only four of these drugs (pioglitazone, tofacitinib, barcitinib and apremilast) have been reported in individual cases or case series of patients with LPP and controlled studies are missing. We describe each drug and mechanism of action target EMT in detail. Although previous studies have demonstrated the efficacy of EMT inhibitors in anticancer therapy, there are, to our knowledge, no studies using EMT-attenuating drugs for the treatment of LPP. The treatment molecules discussed in this paper provide a new platform for clinical studies and controlled trials in LPP.
(© 2022 British Association of Dermatologists.)

Mirmirani P, Willey A, Headington JT et al. Primary cicatricial alopecia: histopathologic findings do not distinguish clinical variants. J Am Acad Dermatol 2005; 52: 637-43.
Karnik P, Tekeste Z, McCormick TS et al. Hair follicle stem cell-specific PPARgamma deletion causes scarring alopecia. J Invest Dermatol 2009; 129: 1243-57.
Imanishi H, Ansell DM, Cheret J et al. Epithelial-to-mesenchymal stem cell transition in a human organ: lessons from lichen planopilaris. J Invest Dermatol 2018; 138: 511-19.
Harries MJ, Meyer K, Chaudhry I et al. Lichen planopilaris is characterized by immune privilege collapse of the hair follicle's epithelial stem cell niche. J Pathol 2013; 231: 236-47.
Harries MJ, Jimenez F, Izeta A et al. Lichen planopilaris and frontal fibrosing alopecia as model epithelial stem cell diseases. Trends Mol Med 2018; 24: 435-48.
Ramesh V, Brabletz T, Ceppi P. Targeting EMT in cancer with repurposed metabolic inhibitors. Trends Cancer 2020; 6: 942-50.
Alam MS, LaBelle B. Treatment of lichen planopilaris with adalimumab in a patient with hidradenitis suppurativa and rheumatoid arthritis. JAAD Case Rep 2020; 6: 219-21.
Wang H, Wang HS, Zhou BH et al. Epithelial-mesenchymal transition (EMT) induced by TNF-α requires AKT/GSK-3β-mediated stabilization of snail in colorectal cancer. PLoS One 2013; 8: e56664.
Kreutzer K, Effendy I. Therapy-resistant folliculitis decalvans and lichen planopilaris successfully treated with adalimumab. J Dtsch Dermatol Ges 2014; 12: 74-6.
Kolosionek E, Savai R, Ghofrani HA et al. Expression and activity of phosphodiesterase isoforms during epithelial mesenchymal transition: the role of phosphodiesterase 4. Mol Biol Cell 2009; 20: 4751-65.
Yeo CD, Kim JW, Ha JH et al. Chemopreventive effect of phosphodieasterase-4 inhibition in benzo(a)pyrene-induced murine lung cancer model. Exp Lung Res 2014; 40: 500-6.
Paton DM. Crisaborole: phosphodiesterase inhibitor for treatment of atopic dermatitis. Drugs Today (Barc) 2017; 53: 239-45.
Fantini A, Demurtas A, Nicoli S et al. In vitro skin retention of crisaborole after topical application. Pharmaceutics 2020; 12: 491.
Tavakolpour S, Mahmoudi H, Abedini R et al. Frontal fibrosing alopecia: an update on the hypothesis of pathogenesis and treatment. Int J Womens Dermatol 2019; 5: 116-23.
Yang CC, Khanna T, Sallee B et al. Tofacitinib for the treatment of lichen planopilaris: a case series. Dermatol Ther 2018; 31: e12656.
Batra P, Sukhdeo K, Shapiro J. Hair loss in lichen planopilaris and frontal fibrosing alopecia: not always irreversible. Skin Appendage Disord 2020; 6: 125-9.
Moussa A, Bhoyrul B, Asfour L et al. Treatment of lichen planopilaris with baricitinib: a retrospective study. J Am Acad Dermatol 2022. https://doi.org/10.1016/j.jaad.2022.02.027.
Kim BS, Howell MD, Sun K et al. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. J Allergy Clin Immunol 2020; 145: 572-82.
Shin JM, Kang JH, Lee SA et al. Effect of doxycycline on epithelial-mesenchymal transition via the p38/Smad pathway in respiratory epithelial cells. Am J Rhinol Allergy 2017; 31: 71-7.
Spencer LA, Hawryluk EB, English JC 3rd. Lichen planopilaris: retrospective study and stepwise therapeutic approach. Arch Dermatol 2009; 145: 333-4.
Tiao J, Goldberg L. The use of doxycycline in lichen planopilaris and frontal fibrosing alopecia: a retrospective study of 138 patients at a tertiary referral clinic. J Am Acad Dermatol 2019; 81: AB135.
Baibergenova A, Walsh S. Use of pioglitazone in patients with lichen planopilaris. J Cutan Med Surg 2012; 16: 97-100.
Mesinkovska NA, Tellez A, Dawes D et al. The use of oral pioglitazone in the treatment of lichen planopilaris. J Am Acad Dermatol 2015; 72: 355-6.
Spring P, Spanou Z, de Viragh PA. Lichen planopilaris treated by the peroxisome proliferator activated receptor-γ agonist pioglitazone: lack of lasting improvement or cure in the majority of patients. J Am Acad Dermatol 2013; 69: 830-2.
Zhao L, Quan Y, Wang J et al. Vitamin C inhibit the proliferation, migration and epithelial-mesenchymal-transition of lens epithelial cells by destabilizing HIF-1α. Int J Clin Exp Med 2015; 8: 15155-63.
Polireddy K, Dong R, Reed G et al. High dose parenteral ascorbate inhibited pancreatic cancer growth and metastasis: mechanisms and a phase I/IIa study. Sci Rep 2017; 7: 17188.
Kirane A, Toombs JE, Larsen JE et al. Epithelial-mesenchymal transition increases tumor sensitivity to COX-2 inhibition by apricoxib. Carcinogenesis 2012; 33: 1639-46.
Adhim Z, Matsuoka T, Bito T et al. In vitro and in vivo inhibitory effect of three Cox-2 inhibitors and epithelial-to-mesenchymal transition in human bladder cancer cell lines. Br J Cancer 2011; 105: 393-402.
Yang T, Chen M, Sun T. Simvastatin attenuates TGF-β1-induced epithelial-mesenchymal transition in human alveolar epithelial cells. Cell Physiol Biochem 2013; 31: 863-74.
Masola V, Zaza G, Secchi MF et al. Heparanase is a key player in renal fibrosis by regulating TGF-β expression and activity. Biochim Biophys Acta 2014; 1843: 2122-8.

Lichen planus follicularis

Date Created: 20220504 Date Completed: 20220822 Latest Revision: 20220822

20250114

10.1111/ced.15245

35506309