A case of rapid improvement of severe psoriasis during molecular-targeted therapy using an epidermal growth factor receptor tyrosine kinase inhibitor for metastatic lung adenocarcinoma

Oyama, Noritaka; Kaneko, Fumio; Togashi, Ari; Yamamoto, Toshiyuki

doi:10.1016/j.jaad.2011.08.009

Cited by 9 publications

(6 citation statements)

References 6 publications

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“…Indeed, EGFR inhibitors improve lesions in patients with psoriasis [46], [47], as also shown in skin lesions of K5.Stat3C mice in the present study. Previous studies demonstrated that topical TPA application led to EGFR activation followed by Stat3 activation in keratinocytes [48].…”

Section: Discussionsupporting

confidence: 86%

Involvement of TNF-α Converting Enzyme in the Development of Psoriasis-Like Lesions in a Mouse Model

et al. 2014

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TNF-α plays a crucial role in psoriasis; therefore, TNF inhibition has become a gold standard for the treatment of psoriasis. TNF-α is processed from a membrane-bound form by TNF-α converting enzyme (TACE) to soluble form, which exerts a number of biological activities. EGF receptor (EGFR) ligands, including heparin-binding EGF-like growth factor (HB-EGF), amphiregulin and transforming growth factor (TGF)-α are also TACE substrates and are psoriasis-associated growth factors. Vascular endothelial growth factor (VEGF), one of the downstream molecules of EGFR and TNF signaling, plays a key role in angiogenesis for developing psoriasis. In the present study, to assess the possible role of TACE in the pathogenesis of psoriasis, we investigated the involvement of TACE in TPA-induced psoriasis-like lesions in K5.Stat3C mice, which represent a mouse model of psoriasis. In this mouse model, TNF-α, amphiregulin, HB-EGF and TGF-α were significantly up-regulated in the skin lesions, similar to human psoriasis. Treatment of K5.Stat3C mice with TNF-α or EGFR inhibitors attenuated the skin lesions, suggesting the roles of TACE substrates in psoriasis. Furthermore, the skin lesions of K5.Stat3C mice showed down-regulation of tissue inhibitor of metalloproteinase-3, an endogenous inhibitor of TACE, and an increase in soluble TNF-α. A TACE inhibitor abrogated EGFR ligand-dependent keratinocyte proliferation and VEGF production in vitro, suggesting that TACE was involved in both epidermal hyperplasia and angiogenesis during psoriasis development. These results strongly suggest that TACE contributes to the development of psoriatic lesions through releasing two kinds of psoriasis mediators, TNF-α and EGFR ligands. Therefore, TACE could be a potential therapeutic target for the treatment of psoriasis.

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Section: Discussionsupporting

confidence: 86%

Involvement of TNF-α Converting Enzyme in the Development of Psoriasis-Like Lesions in a Mouse Model

et al. 2014

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“…Researchers have reported that psoriasis-associated inflammation remitted spontaneously in lung cancer patients who were undergoing chemotherapy with erlotinib [10,11]. Additionally, Onyama et al have reported of a patient presenting with metastatic lung adenocarcinoma who exhibited severe psoriatic skin lesions that decreased significantly after onset of oral administration of erlotinib [12]. However, the patient experienced acneform eruptions and a rash in the seborrheic areas, which are consistent with the adverse reactions of tyrosine kinase inhibitors.…”

Section: Introductionmentioning

confidence: 72%

Novel amphiphilic lipid augments the co-delivery of erlotinib and IL36 siRNA into the skin for psoriasis treatment

Boakye

Patel

Doddapaneni

et al. 2017

Journal of Controlled Release

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In this study, we demonstrate for the first time the concurrent transdermal delivery of erlotinib and IL36α siRNA as a potential dual therapy for psoriasis. The objectives were to develop and evaluate lipid nanocarriers (CYnLIP) using a novel pyrrolidinium lipid to disrupt the skin barrier for enhanced transdermal delivery. CYnLIP (132.00±6.23nm) had encapsulation efficiency of 49.04±2.54% for erlotinib. DSC confirmed encapsulation of erlotinib within CYnLIP. Atomic Force Microscopy demonstrated notable topographical changes in the stratum corneum of skin permeated with CYnLIP that were absent in skin hydrated with water. Peak force distance curves also exhibited a more permeable membrane for CYnLIP-incubated skin than hydrated skin. Permeation studies showed enhanced (p<0.01) skin retention of erlotinib by CYnLIP (40.76-fold) than solution and more pronounced fluorescence at deeper layers of the skin for fluorescein-labeled siRNA-CYnLIP than solution. The enhanced co-transdermal delivery of erlotinib and IL36α siRNA by CYnLIP efficaciously treated psoriatic-like plaques in C57BL/6 mice (PASI score of 1) compared to imiquimod-only treatment (PASI score of 4). IHC and western blotting revealed reduction in epidermal hyperplasia (Ki67) and in the dermal infiltration of inflammatory cytokines (IL36α, pSTAT3, TNFα, NFκB, IL23 and IL17) for erlotinib/IL36α siRNA-CYnLIP (p<0.05) comparable to Tacrolimus but markedly less than imiquimod-only treatment.

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“…EGFR expressed mostly by basal keratinocytes is not upregulated in psoriatic lesions (28,45). Moreover, EGFR kinases inhibitors used as cancer therapy such as Erlotinib, Lapatinib and monoclonal antibodies targeting the extracellular domain of EGFR including Cetuximab were shown to improve psoriatic lesions in cancer patients (46)(47)(48)(49)(50). We observed that EGFR kinase inhibitor AG1478 also decreased Aldara ® -induced acanthosis, suggesting that this pathway is also involved in this experimental setting.…”

Section: Discussionmentioning

confidence: 70%

JNK1 Signaling Downstream of the EGFR Pathway Contributes to Aldara®-Induced Skin Inflammation

Azouz

Thomas

et al. 2021

Front. Immunol.

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c-Jun N-terminal protein kinase 1 (JNK1) is involved in multiple biological processes but its implication in inflammatory skin diseases is still poorly defined. Herein, we studied the role of JNK1 in the context of Aldara®-induced skin inflammation. We observed that constitutive ablation of JNK1 reduced Aldara®-induced acanthosis and expression of inflammatory markers. Conditional deletion of JNK1 in myeloid cells led to reduced skin inflammation, a finding that was associated with impaired Aldara®-induced inflammasome activation in vitro. Next, we evaluated the specific role of JNK1 in epidermal cells. We observed reduced Aldara®-induced acanthosis despite similar levels of inflammatory markers. Transcriptomic and epigenomic analysis of keratinocytes revealed the potential involvement of JNK1 in the EGFR signaling pathway. Finally, we show that inhibition of the EGFR pathway reduced Aldara®-induced acanthosis. Taken together, these data indicate that JNK1 plays a dual role in the context of psoriasis by regulating the production of inflammatory cytokines by myeloid cells and the sensitivity of keratinocytes to EGFR ligands. These results suggest that JNK1 could represent a valuable therapeutic target in the context of psoriasis.

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A case of rapid improvement of severe psoriasis during molecular-targeted therapy using an epidermal growth factor receptor tyrosine kinase inhibitor for metastatic lung adenocarcinoma

Cited by 9 publications

References 6 publications

Involvement of TNF-α Converting Enzyme in the Development of Psoriasis-Like Lesions in a Mouse Model

Involvement of TNF-α Converting Enzyme in the Development of Psoriasis-Like Lesions in a Mouse Model

Novel amphiphilic lipid augments the co-delivery of erlotinib and IL36 siRNA into the skin for psoriasis treatment

JNK1 Signaling Downstream of the EGFR Pathway Contributes to Aldara®-Induced Skin Inflammation

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