The Koebner-Phenomenon in Epidermal Growth Factor Receptor Inhibitor–Induced Cutaneous Adverse Effects

Gerber, Peter Arne; Enderlein, Elaine; Homey, Bernhard

doi:10.1200/jco.2007.16.0077

Cited by 20 publications

(16 citation statements)

References 34 publications

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“…In cutaneous wound healing, EGF regulates fibroblast mobility and proliferation during all stages of wound healing, suggesting that it plays critical roles in coordinating wound repair through ECM remodeling (37,38). Specifically, the loss of proliferative and migratory activity of aging fibroblasts coupled with the loss of wound closure ability and skin repair leads to a high risk of barrier disruption by surgical wound rupture and infection (17,39). Thus, the EGF-induced migration and proliferation through the recovered levels of EGFR in aged fibroblasts has been suggested as a potential therapy for wound healing and skin recovery (40).…”

Section: Discussionmentioning

confidence: 99%

Epidermal growth factor improves the migration and contractility of aged fibroblasts cultured on 3D collagen matrices

Kim

Mun

et al. 2015

International Journal of Molecular Medicine

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Abstract. Epidermal growth factor (EGF) plays a critical role in fibroblasts by stimulating the production of collagen and supports cell renewal through the interaction between keratinocytes and fibroblasts. It is well known that the contractile activity of fibroblasts is required for the remodeling of the extracellular matrix (ECM), which contributes to skin elasticity. However, the role of EGF in the contraction of aged fibroblasts under 3-dimensional (3D) culture conditions is not yet fully understood. In the present study, we demonstrated that young fibroblasts spread and proliferated more rapidly than aged fibroblasts under 2-dimensional (2D) culture conditions. Cell migration assay using a nested collagen matrix revealed that the migration of young fibroblasts was also greater than that of aged fibroblasts under 3D culture conditions. However, the addition of recombinant human EGF (rhEGF) resulted in the enhanced migration of aged fibroblasts; the migration rate was similar to that of the young fibroblasts. The aged fibroblasts showed decreased cluster formation compared with the young fibroblasts on the collagen matrix, which was improved by the addition of rhEGF. Furthermore, cell contraction assay revealed that the basal contractility of the aged fibroblasts was lower than that of the young fibroblasts; however, following treatment with rhEGF, the contractility was restored to levels similar or even higher to those of the young fibroblasts. Taken together, our results suggest that rhEGF is a potential renewal agent that acts to improve the migration and contraction of aged fibroblasts more efficiently than young fibroblasts under 3D culture conditions; thus, EGF may have valuable regenerative effects on aged skin. IntroductionSkin aging is a biological process that involves cutaneous aging and photo-aging, both of which are associated with harmful environmental insults, including UV radiation, heat, gravity and smoking (1). More specifically, cutaneous aging comprises the loss of elasticity, which causes wrinkling of the skin through the deprivation of extracellular matrix (ECM) (2,3). Treatments for skin aging include herbal extracts, vitamins and growth factors, which have been established to promote ECM protein synthesis and to reduce degradation enzymes of the ECM, thereby delaying the progression of skin aging (4-6).Several growth factors and cytokines are involved in the regulation of skin homeostasis and development (7), all of which are important for the preservation of cutaneous functions by acting as autocrine and paracrine factors (8). Furthermore, several recombinant cytokines and growth factors are currently used in clinical practice to treat patients with various diseases. These cytokines and growth factors control the regulatory functions of several powerful and complex signaling networks. Among these, the epidermal growth factor (EGF) and its receptor (EGFR) command a wide spectrum of diverse biological effects, including cellular proliferation, differentiation, wound healing, hair folli...

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Section: Discussionmentioning

confidence: 99%

Epidermal growth factor improves the migration and contractility of aged fibroblasts cultured on 3D collagen matrices

Kim

Mun

et al. 2015

International Journal of Molecular Medicine

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“…Likewise, increased numbers of DF may represent inflammatory stimuli that suffice to worsen the clinical picture of EGFRI rashes. These stimuli may support the development of new or aggravation of existing lesions by koebnerization [32]. …”

Section: Discussionmentioning

confidence: 99%

Density of <i>Demodex folliculorum</i> in Patients Receiving Epidermal Growth Factor Receptor Inhibitors

et al. 2011

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Background: Rosacea-like papulopustular eruptions (rash) are considered the most frequent toxicities associated with the use of inhibitors of the epidermal growth factor receptor (EGFR). Recently, evidence has been accumulating of infectious complications in patients suffering from these adverse effects. Objective: We sought to analyze the density of Demodex folliculorum (DF) in cutaneous lesions of patients presenting with EGFR-inhibitor (EGFRI)-induced rashes. Methods: This is a retrospective study of 19 adult patients presenting with EGFRI rashes. Patients were reviewed for the density of DF (Demodex density, Dd; mites per square centimeter) by standardized skin surface biopsy. Results: In our patient collective the mean Dd of 4.7/cm² significantly exceeded the mean Dd reported for the healthy adult population (Dd = 0.7/cm²). Limitations: The retrospective nature of the study. Conclusions: EGFRI patients have an increased susceptibility to DF colonization or infection, respectively. Our results support the recent concept that EGFRI may induce an impairment of antimicrobial defense mechanisms.

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“…In fact, we could show that the combination of nadifloxacin 1% cream and prednicarbate 0.25% cream significantly improved rash severity. In this context the management of cutaneous infections is also likely to exert protective effects regarding the aggravation of skin inflammation as infectious agents may trigger inflammatory rash progression by means of "Koebnerization" [33]. Systemic isotretinoin, finally, is recommended for the management of severe EGFRI rashes of rashes that do not respond to other therapies [23].…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, current studies report promising results on the clinical effectiveness of drugs that target the EGFR-signaling cascade, such as the BRAF inhibitor vemurafenib or MEK inhibitors [2]. Characteristic inflammatory papulopustular exanthemas, often described as acneiform or rosaceaform rashes, are the most frequent adverse effect associated with the use of EGFR-inhibtors (EGFRI) [3][4][5][6]. Within the first days to weeks of therapy > 90% of patients develop these rashes.…”

Section: Introductionmentioning

confidence: 99%

Management of EGFR-inhibitor associated rash: A retrospective study in 49 patients

et al. 2012

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Background: In recent years inhibitors directed against the epidermal growth factor receptor (EGFR) have evolved as effective targeting cancer drugs. Characteristic papulopustular exanthemas, often described as acneiform rashes, are the most frequent adverse effect associated with this class of novel cancer drugs and develop in > 90% of patients. Notably, the rash may significantly compromise the patients' quality of life, thereby potentially leading to incompliance as well as dose reduction or even termination of the anti-EGFR therapy. Yet, an effective dermatologic management of cutaneous adverse effects can be achieved. Whereas various case reports, case series or expert opinions on the management of EGFR-inhibitor (EGFRI) induced rashes have been published, data on systematic management studies are sparse.

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The Koebner-Phenomenon in Epidermal Growth Factor Receptor Inhibitor–Induced Cutaneous Adverse Effects

Abstract: Hepatic arterial infusion chemotherapy through a port-catheter system as preoperative initial therapy in patients with advanced liver dysfunction due to synchronous and unresectable liver metastases from colorectal cancer.

Cited by 20 publications

References 34 publications

Epidermal growth factor improves the migration and contractility of aged fibroblasts cultured on 3D collagen matrices

Epidermal growth factor improves the migration and contractility of aged fibroblasts cultured on 3D collagen matrices

Density of <i>Demodex folliculorum</i> in Patients Receiving Epidermal Growth Factor Receptor Inhibitors

Management of EGFR-inhibitor associated rash: A retrospective study in 49 patients

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