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https://www.readbyqxmd.com/read/27912760/update-on-recent-preclinical-and-clinical-studies-of-t790m-mutant-specific-irreversible-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors
#1
REVIEW
Bin-Chi Liao, Chia-Chi Lin, Jih-Hsiang Lee, James Chih-Hsin Yang
The first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (1/2G EGFR-TKIs) gefitinib, erlotinib, and afatinib have all been approved as standard first-line treatments for advanced EGFR mutation-positive non-small cell lung cancer. The third-generation (3G) EGFR-TKIs have been developed to overcome the EGFR T790M mutation, which is the most common mechanism of acquired resistance to 1/2G EGFR-TKI treatment. This resistance mutation develops in half of the patients who respond to 1/2G EGFR-TKI therapy...
December 3, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27893423/efficacy-and-safety-of-icotinib-in-treating-non-small-cell-lung-cancer-a-systematic-evaluation-and-meta-analysis-based-on-15-studies
#2
Rong Biaoxue, Liu Hua, Gao Wenlong, Yang Shuanying
Icotinib is a new epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that developed and used in China; this work was to evaluate its efficacy and safety in treating non-small cell lung cancer (NSCLC). Clinical studies evaluating the efficacy and safety of icotinib in treating NSCLC were identified from the databases of Medline, Web of Science, Embase and Cochrance Library. Pooled efficacy and safety of icotinib were calculated through a series of predefined search strategies. A total of 15 studies with 2,304 patients were involved in this study...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27836854/a-novel-spectroscopically-determined-pharmacodynamic-biomarker-for-skin-toxicity-in-cancer-patients-treated-with-targeted-agents
#3
Antoine Azan, Peter J Caspers, Tom C Bakker Schut, Séverine Roy, Céline Boutros, Christine Mateus, Emilie Routier, Benjamin Besse, David Planchard, Atmane Seck, Nyam Kamsu-Kom, Gorana Tomasic, Senada Koljenović, Vincent Noordhoek Hegt, Texier Matthieu, Emilie Lanoy, Alexander M Eggermont, Angelo Paci, Caroline Robert, Gerwin J Puppels, Lluis M Mir
Raman spectroscopy is a non-invasive and label-free optical technique that provides detailed information about the molecular composition of a sample. In this study, we evaluated the potential of Raman spectroscopy to predict skin toxicity due to tyrosine-kinase inhibitors treatment. We acquired Raman spectra of skin of patients undergoing treatment with MEK, EGFR or BRAF inhibitors which are known to induce severe skin toxicity; for this pilot study, three patients were included for each inhibitor. Our algorithm, based on Partial Least Squares-Discriminant Analysis (PLS-DA) and cross-validation by bootstrapping, discriminated to variable degrees spectra from patient suffering and not suffering cutaneous adverse events...
November 11, 2016: Cancer Research
https://www.readbyqxmd.com/read/27833902/minocycline-improves-the-efficacy-of-egfr-inhibitor-therapy-a-hypothesis
#4
Ajit Venniyoor, Bassim Al Bahrani
Skin rash is a side effect of drugs that inhibit epithelial growth factor receptor (EGFR) as a part of targeted therapy of cancer. Its appearance and severity correlates with survival. Minocycline, an oral tetracycline antibiotic, is recommended as treatment (and increasingly, for prevention) of the rash, though infection is seen in only one-third of the patients. Minocycline has additional anticancer properties such as poly(ADP-ribose) polymerase inhibition. It is proposed that such properties contribute to the efficacy of EGFR inhibitors and can also explain the positive correlation between grade of rash and survival as patients with higher grades of rash are more likely to receive minocycline...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27825616/vandetanib-in-patients-with-previously-treated-ret-rearranged-advanced-non-small-cell-lung-cancer-luret-an-open-label-multicentre-phase-2-trial
#5
Kiyotaka Yoh, Takashi Seto, Miyako Satouchi, Makoto Nishio, Noboru Yamamoto, Haruyasu Murakami, Naoyuki Nogami, Shingo Matsumoto, Takashi Kohno, Koji Tsuta, Katsuya Tsuchihara, Genichiro Ishii, Shogo Nomura, Akihiro Sato, Atsushi Ohtsu, Yuichiro Ohe, Koichi Goto
BACKGROUND: RET rearrangements are rare oncogenic alterations in non-small-cell lung cancer (NSCLC). Vandetanib is a multitargeted tyrosine kinase inhibitor exhibiting RET kinase activity. We aimed to assess the efficacy and safety of vandetanib in patients with advanced RET-rearranged NSCLC. METHODS: In this open-label, multicentre, phase 2 trial (LURET), patients with advanced RET-rearranged NSCLC continuously received 300 mg of oral vandetanib daily. RET-positive patients were screened using a nationwide genomic screening network of about 200 participating institutions...
November 4, 2016: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/27791234/cutaneous-toxicity-from-epidermal-growth-factor-receptor-inhibitors-would-a-subcutaneous-desensitization-be-helpful-case-report
#6
Andrea D'Alessio, Sara Cecchini, Daniela Di Mauro, Luca Geroli, Simonetta Villa, Antonello Quadri, Davide Resta, Carmelo Fortugno
PURPOSE: Cetuximab and panitumumab are monoclonal antibody inhibitors that bind the epidermal growth factor receptor (EGFR) currently used in the treatment of metastatic colorectal cancer. The main adverse event related to EGFR inhibitors (EGFR-Is) is cutaneous toxicity, which can cause dosage reduction and interruption of treatment. State-of-the-art management of skin toxicity associated with EGFR-Is therapy involves the topical administration of corticosteroids and oral antibiotics, but is not completely effective in the management of toxicity...
October 26, 2016: Tumori
https://www.readbyqxmd.com/read/27766784/retrospective-study-of-adjuvant-icotinib-in-postoperative-lung-cancer-patients-harboring-epidermal-growth-factor-receptor-mutations
#7
Shuyang Yao, Xiuyi Zhi, Ruotian Wang, Kun Qian, Mu Hu, Yi Zhang
BACKGROUND: Epidermal growth factor receptor (EGFR) mutations occur in about 50% of Asian patients with non-small cell lung cancer (NSCLC). Patients with advanced NSCLC and EGFR mutations derive clinical benefit from treatment with EGFR-tyrosine kinase inhibitors (TKIs). This study assessed the efficacy and safety of adjuvant icotinib without chemotherapy in EGFR-mutated NSCLC patients undergoing resection of stage IB-IIIA. METHODS: Our retrospective study enrolled 20 patients treated with icotinib as adjuvant therapy...
September 2016: Thoracic Cancer
https://www.readbyqxmd.com/read/27755795/lung-squamous-cell-carcinoma-with-brachial-soft-tissue-metastasis-responsive-to-gefitinib-report-of-a-rare-case
#8
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
https://www.readbyqxmd.com/read/27725919/afatinib-associated-cutaneous-toxicity-a-correlation-of-severe-skin-reaction-with-dramatic-tumor-response-in-a-woman-with-exon-19-deletion-positive-non-small-cell-lung-cancer
#9
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
https://www.readbyqxmd.com/read/27720938/identification-of-gene-expression-profiling-associated-with-erlotinib-related-skin-toxicity-in-pancreatic-adenocarcinoma-patients
#10
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
https://www.readbyqxmd.com/read/27718067/dermatologic-events-from-egfr-inhibitors-the-issue-of-the-missing-patient-voice
#11
Bernd Tischer, Renate Huber, Matthias Kraemer, Mario E Lacouture
PURPOSE: As epidermal growth factor receptor (EGFR) inhibitors are associated with a variety of dermatologic adverse events (dAEs), the purpose of this study was to develop an overview of current knowledge of dAEs associated with EGFR inhibitors and to identify knowledge gaps regarding incidence, treatment, impact on quality of life (QOL), and patient acceptance. METHOD: A structured literature search was conducted using MEDLINE/PubMed (January 1983 to January 2014)...
October 7, 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/27680009/-cutaneous-squamous-cell-carcinoma
#12
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
https://www.readbyqxmd.com/read/27668532/anti-proliferation-effects-efficacy-of-cyasterone-in-vitro-and-in-vivo-and-its-mechanism
#13
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
https://www.readbyqxmd.com/read/27641462/-osimertinib-tagrisso-%C3%A2-activity-indication-and-modality-of-use-in-non-small-cell-lung-cancer
#14
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
https://www.readbyqxmd.com/read/27630354/appetite-loss-as-an-adverse-effect-during-treatment-with-egfr-tkis-in-elderly-patients-with-non-small-cell-lung-cancer
#15
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
https://www.readbyqxmd.com/read/27614311/improved-transduction-efficiencies-of-adeno-associated-virus-vectors-by-synthetic-cell-permeable-peptides
#16
Kitako Tabata, Eriko Sugano, Fumika Murakami, Tetsuro Yamashita, Taku Ozaki, Hiroshi Tomita
Various serotypes of adeno-associated virus (AAV) vectors have been used for gene therapy and as research tools. Among these serotypes, the AAV type 2 vector has been used successfully in human gene therapies. However, the transduction efficiency of AAV2 depends on the cell type, and this poses a problem in the efficacy of gene therapy. To improve the transduction efficiency of AAV2, we designed a small peptide consisting of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor peptide and the HIV-Tat sequence Tat-Y1068...
September 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27588390/a-decrease-in-d-dimer-concentration-and-an-occurrence-of-skin-rash-as-iatrogenic-events-and-complementary-predictors-of-survival-in-lung-cancer-patients-treated-with-egfr-tyrosine-kinase-inhibitors
#17
Magdalena Zaborowska-Szmit, Dariusz M Kowalski, Aleksandra Piórek, Maciej Krzakowski, Sebastian Szmit
BACKGROUND: Progression of lung cancer is associated with some abnormalities in coagulation. The aim of the study was to determine the predictive and prognostic value of changes in D-dimer concentration in non-small cell lung cancer (NSCLC) patients on anti-EGFR targeted therapy. METHODS: The analysis included fifty two NSCLC patients treated with EGFR tyrosine kinase inhibitors (TKIs): erlotinib or gefitinib. All clinical data were collected before treatment and after 2 cycles (60days) of therapy and correlated with progression free and overall survival (PFS, OS)...
July 20, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27565916/successful-oral-desensitization-against-skin-rash-induced-by-alectinib-in-a-patient-with-anaplastic-lymphoma-kinase-positive-lung-adenocarcinoma-a-case-report
#18
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
https://www.readbyqxmd.com/read/27513608/the-role-of-rnase-7-in-innate-cutaneous-defense-against-pseudomonas-aeruginosa
#19
Franziska Rademacher, Maren Simanski, Lena Schröder, Michael Mildner, Jürgen Harder
The ribonuclease RNase 7 is a major skin-derived human antimicrobial protein expressed in keratinocytes. Here we show that the gram-negative pathogen Pseudomonas aeruginosa secretes factor(s) that induced RNase 7 gene and protein expression in human primary keratinocytes. The metalloprotease inhibitor marimastat, the epidermal growth factor receptor (EGFR) inhibitor AG1478 and the EGFR blocking antibody cetuximab significantly attenuated this induction indicating an important role of the EGFR for the P. aeruginosa-mediated RNase 7 induction...
August 11, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27467256/immune-modulation-by-epidermal-growth-factor-receptor-inhibitors-implication-on-anti-tumor-immunity-in-lung-cancer
#20
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
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