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EGFR inhibitor skin effect

Kana Kataoka, Eiji Osaka, Tetsuo Shimizu, Yuki Okamura, Yukihiro Yoshida, Yasuaki Tokuhashi
Metastasis of lung cancer to soft tissue is rare and patient outcomes are generally poor. There are no reports describing soft tissue metastasis in lung squamous cell carcinoma (SCC), in which gefitinib treatment was effective not only for the primary tumor but also the metastatic lesion. A 61-year-old Asian woman presented to our facility with pain and a mass in the brachium. An additional tumor was identified in the lung. As we suspected soft tissue metastasis of lung cancer, an incisional biopsy was performed, yielding a diagnosis of SCC...
June 13, 2016: Thoracic Cancer
Lindsay P Osborn, Philip R Cohen
Epidermal growth factor receptor (EGFR) inhibitors are biological factors used in the treatment of non-small-cell lung cancers (NSCLC) that are positive for EGFR mutations. Afatinib is one such drug that has been approved for use in this capacity. Cutaneous toxicity is the second most commonly reported adverse event with the use of afatinib. A 39-year-old woman with inoperative right lung adenocarcinoma was initially treated with afatinib. She not only developed a severe papulopustular eruption but also had a dramatic reduction of her tumor...
September 1, 2016: Curēus
Octavio Caba, Antonio Irigoyen, Cristina Jimenez-Luna, Manuel Benavides, Francisco M Ortuño, Javier Gallego, Ignacio Rojas, Carmen Guillen-Ponce, Carolina Torres, Enrique Aranda, Jose Prados
Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that showed activity against pancreatic ductal adenocarcinoma (PDAC). The drug's most frequently reported side effect as a result of EGFR inhibition is skin rash (SR), a symptom which has been associated with a better therapeutic response to the drug. Gene expression profiling can be used as a tool to predict which patients will develop this important cutaneous manifestation. The aim of the present study was to identify which genes may influence the appearance of SR in PDAC patients...
October 6, 2016: Toxicology and Applied Pharmacology
U Leiter, R Gutzmer, M Alter, C Ulrich, A S Lonsdorf, M M Sachse, U Hillen
Squamous cell carcinoma (SCC) of the skin accounts for 20 % of non-melanoma skin cancer and is one of the most frequent types of cancer in Caucasian populations. Diagnosis is based on the clinical features and should be histopathologically confirmed to adequately address the prognosis and treatment. Complete surgical excision with histopathological control of excision margins is the gold standard in the treatment of primary SCC. Sentinel lymph node biopsies (SLNB) can be considered in SCC with a tumor thickness of >6 mm but there is currently no evidence concerning prognostic and therapeutic effects...
September 28, 2016: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
XinGang Lu, HongFu Qiu, Liu Yang, JieYing Zhang, ShuJie Ma, Lan Zhen
Cyasterone was demonstrated potential inhibition effect in mouse skin carcinoma cells in published report. However, the molecular mechanisms of the cyasterone on cells remain unknown. Herein, we investigated the effects of cyasterone-induced apoptosis in A549 and MGC823 cells in vitro. MTT assay showed that cyasterone caused a significantly decreasing of the proliferation of A549 and MGC823 cells in a time-and dose-dependent manner with IC50 values of 38.50±3.73μg/mL on A549 cells and 32.96±1.24μg/mL on MGC823 cells at 48h, respectively...
September 23, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Etienne Giroux Leprieur, Alexis B Cortot, Jacques Cadranel, Marie Wislez
The acquisition of a resistance EGFR mutation in exon 20 (T790M) occurs in half of the cases of secondary resistance to EGFR tyrosine kinase inhibitors (TKI), given in first-line treatment in advanced EGFR-mutated non-small cell lung cancers (NSCLC). Osimertinib (AZD9291, Tagrisso(®)) is a third-generation, irreversible EGFR TKI, active in case of T790M mutation. A large phase I trial showed the efficacy of osimertinib after failure of first-generation EGFR TKI (erlotinib, gefitinib), with response rate at 51% and up to 61% in case of T790M mutation...
September 15, 2016: Bulletin du Cancer
Minehiko Inomata, Kazuki Shimokawa, Kotaro Tokui, Chihiro Taka, Seisuke Okazawa, Kenta Kambara, Toru Yamada, Toshiro Miwa, Ryuji Hayashi, Tatsuhiko Kashii, Shoko Matsui, Kazuyuki Tobe
AIM: We conducted a retrospective study to investigate the frequency of appetite loss during treatment with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in elderly patients, aged 75 years or older, with non-small cell lung cancer harboring EGFR gene mutations. PATIENTS AND METHODS: Data of a total of 64 patients, including 39 relatively young (hereinafter, younger) patients and 25 elderly patients were analyzed. RESULTS: Appetite loss of all grades (p=0...
September 2016: Anticancer Research
Masayuki Shirasawa, Masaru Kubotaa, Shinya Harada, Hideyuki Niwa, Seiichiro Kusuhara, Masashi Kasajima, Yasuhiro Hiyoshi, Mikiko Ishihara, Satoshi Igawa, Noriyuki Masuda
Alectinib has been approved for the treatment of patients with anaplastic lymphoma kinase (ALK) gene rearrangement-positive advanced non-small cell lung cancer. In terms of adverse effects, the occurrence of a severe skin rash induced by alectinib is reportedly rare, compared with the occurrence of skin rash induced by epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). In the present case report, a 76-year-old woman with ALK-positive lung adenocarcinoma experienced disease progression after undergoing first-line chemotherapy...
September 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Jin S Im, Amanda C Herrmann, Chantale Bernatchez, Cara Haymaker, Jeffrey J Molldrem, Waun Ki Hong, Roman Perez-Soler
Skin toxicity is the most common toxicity caused by Epidermal Growth Factor Receptor (EGFR) inhibitors, and has been associated with clinical efficacy. As EGFR inhibitors enhance the expression of antigen presenting molecules in affected skin keratinocytes, they may concurrently facilitate neo-antigen presentation in lung cancer tumor cells contributing to anti-tumor immunity. Here, we investigated the modulatory effect of the EGFR inhibitor, erlotinib on antigen presenting molecules and PD-L1, prominent immune checkpoint protein, of skin keratinocytes and lung cancer cell lines to delineate the link between EGFR signaling pathway inhibition and potential anti-tumor immunity...
2016: PloS One
Ralf-Dieter Hofheinz, Gaël Deplanque, Yoshito Komatsu, Yoshimitsu Kobayashi, Janja Ocvirk, Patrizia Racca, Silke Guenther, Jun Zhang, Mario E Lacouture, Aminah Jatoi
: : Inhibition of the epidermal growth factor receptor (EGFR) is an established treatment that extends patient survival across a variety of tumor types. EGFR inhibitors fall into two main categories: anti-EGFR monoclonal antibodies, such as cetuximab and panitumumab, and first-generation tyrosine kinase inhibitors, such as afatinib, gefitinib, and erlotinib. Skin reactions are the most common EGFR inhibitor-attributable adverse event, resulting in papulopustular (acneiform) eruptions that can be painful and debilitating, and which may potentially have a negative impact on patients' quality of life and social functioning, as well as a negative impact on treatment duration...
July 22, 2016: Oncologist
Silvana Sandri, Fernanda Faião-Flores, Manoela Tiago, Paula Comune Pennacchi, Renato Ramos Massaro, Débora Kristina Alves-Fernandes, Gustavo Noriz Berardinelli, Adriane Feijó Evangelista, Vinicius de Lima Vazquez, Rui Manuel Reis, Silvya Stuchi Maria-Engler
The BRAF(V600E) mutation confers constitutive kinase activity and accounts for >90% of BRAF mutations in melanoma. This genetic alteration is a current therapeutic target; however, the antitumorigenic effects of the BRAF(V600E) inhibitor vemurafenib are short-lived and the majority of patients present tumor relapse in a short period after treatment. Characterization of vemurafenib resistance has been essential to the efficacy of next generation therapeutic strategies. Herein, we found that acute BRAF inhibition induced a decrease in active MMP-2, MT1-MMP and MMP-9, but did not modulate the metalloproteinase inhibitors TIMP-2 or RECK in naïve melanoma cells...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Daniela Lulli, Maria Luigia Carbone, Saveria Pastore
The Epidermal Growth Factor Receptor (EGFR) is centrally involved in the regulation of key processes of the epithelia, including cell proliferation, survival, differentiation, and also tumorigenesis. Humanized antibodies and small-molecule inhibitors targeting EGFR were developed to disrupt these functions in cancer cells and are currently used in the treatment of diverse metastatic epithelial cancers. By contrast, these drugs possess significant skin-specific toxic effects, comprising the establishment of a persistent inflammatory milieu...
June 14, 2016: Oncotarget
Martin Holcmann, Maria Sibilia
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is frequently mutated or overexpressed in a large number of tumors such as carcinomas or glioblastoma. Inhibitors of EGFR activation have been successfully established for the therapy of some cancers and are more and more frequently being used as first or later line therapies. Although the side effects induced by inhibitors of EGFR are less severe than those observed with classic cytotoxic chemotherapy and can usually be handled by out-patient care, they may still be a cause for dose reduction or discontinuation of treatment that can reduce the effectiveness of antitumor therapy...
October 2015: Molecular & Cellular Oncology
Sheri L Moores, Mark L Chiu, Barbara S Bushey, Kristen Chevalier, Leopoldo Luistro, Keri Dorn, Randall J Brezski, Peter Haytko, Thomas Kelly, Sheng-Jiun Wu, Pauline L Martin, Joost Neijssen, Paul W H I Parren, Janine Schuurman, Ricardo M Attar, Sylvie Laquerre, Matthew V Lorenzi, G Mark Anderson
Non-small cell lung cancers (NSCLC) with activating EGFR mutations become resistant to tyrosine kinase inhibitors (TKI), often through second-site mutations in EGFR (T790M) and/or activation of the cMet pathway. We engineered a bispecific EGFR-cMet antibody (JNJ-61186372) with multiple mechanisms of action to inhibit primary/secondary EGFR mutations and the cMet pathway. JNJ-61186372 blocked ligand-induced phosphorylation of EGFR and cMet and inhibited phospho-ERK and phospho-AKT more potently than the combination of single receptor-binding antibodies...
July 1, 2016: Cancer Research
Xiaochen Zhou, Mingjia Tan, Mukesh K Nyati, Yongchao Zhao, Gongxian Wang, Yi Sun
MLN4924, also known as pevonedistat, is the first-in-class inhibitor of NEDD8-activating enzyme, which blocks the entire neddylation modification of proteins. Previous preclinical studies and current clinical trials have been exclusively focused on its anticancer property. Unexpectedly, we show here, to our knowledge for the first time, that MLN4924, when applied at nanomolar concentrations, significantly stimulates in vitro tumor sphere formation and in vivo tumorigenesis and differentiation of human cancer cells and mouse embryonic stem cells...
May 24, 2016: Proceedings of the National Academy of Sciences of the United States of America
Daška Štulhofer Buzina, Ivana Martinac, Daniela Ledić Drvar, Romana Čeović, Ivan Bilić, Branka Marinović
Dear Editor, Inhibition of the epidermal growth factor receptor (EGFR) is a new strategy in treatment of a variety of solid tumors, such as colorectal carcinoma, non-small cell lung cancer, squamous cell carcinoma of the head and neck, and pancreatic cancer (1). Cetuximab is a chimeric human-murine monoclonal antibody against EGFR. Cutaneous side effects are the most common adverse reactions occurring during epidermal growth factor receptor inhibitors (EGFRI) therapy. Papulopustular rash (acne like rash) develop with 80-86% patients receiving cetuximab, while xerosis, eczema, fissures, teleangiectasiae, hyperpigmentations, and nail and hair changes occur less frequently (2)...
April 2016: Acta Dermatovenerologica Croatica: ADC
Saida Rezaković, Zrinjka Paštar, Zrinka Bukvić Mokos, Gordana Pavliša, Suzana Kovačević
Skin and skin adnexa toxicities are the most common side effects associated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and occur in most patients receiving this therapy. The majority of these cutaneous side effects are transient, reversible, and dose dependent. Although these symptoms are in general not severe, they significantly affect quality of life and can have a serious effect on treatment compliance as well as the treatment regimen. The most common early symptoms present as papulopustules on an erythematous base, usually localized in seborrheic areas...
April 2016: Acta Dermatovenerologica Croatica: ADC
P Parikh, K Prabhash, R Naik, A K Vaid, C Goswami, S Rajappa, V Noronha, A Joshi, R T Chacko, S Aggarwal, D C Doval
Tyrosine kinase inhibitors (TKIs) are a pharmaceutical class of small molecules, orally available with manageable safety profile, approved worldwide for the treatment of several neoplasms, including lung, breast, kidney and pancreatic cancer as well as gastro-intestinal stromal tumours and chronic myeloid leukaemia. In recent years, management of lung cancer has been moving towards molecular-guided treatment, and the best example of this new approach is the use of the tyrosine kinase inhibitors (TKIs) in patients with mutations in the epidermal growth factor receptor (EGFR)...
January 2016: Indian Journal of Cancer
Joong Woon Choi, Tae In Kim, Ki-Heon Jeong, Min Kyung Shin
Epidermal growth factor receptor (EGFR) inhibitor, a targeted therapy in the field of oncology, is a new drugs suggested for the cause of acneiform eruptions. The unresponsiveness to conventional acne therapy is a pivotal reason of seeking alternatives to treat drug-induced acneiform eruptions. A 30-year-old female treated with cetuximab, EGFR inhibitor presented with numerous sized erythematous papules and pustules on her face. All responses of oral medications and topical application were poor. She was treated with two passes of non-ablative 1550 nm fractional erbium glass laser with topical clindamycin...
July 2016: Dermatologic Therapy
Xiaowen Jiang, Wenxian Wang, Yiping Zhang
BACKGROUND: Targeted therapy has become an indispensable therapy method in advanced non-small cell lung cancer (NSCLC) treatment. Epithelial growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) can significantly prolong the survival of patients harboring EGFR gene mutation. Icotinb is China's first EGFR-TKI with independent intellectual property rights. The aim of this study is to investigate the clinical characteristics about the beneficiary of advanced NSCLC patients with EGFR Common mutation who were treated with Icotinib...
April 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
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