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https://www.readbyqxmd.com/read/28901517/cx32-inhibits-tnf%C3%AE-induced-extrinsic-apoptosis-with-and-without-egfr-suppression
#1
Yongchang Lai, Liang Tao, Yifan Zhao, Xiaomin Zhang, Xingjuan Sun, Qin Wang, Chengfang Xu
Tumor necrosis factor α (TNFα) and TNF-related apoptosis-inducing ligand (TRAIL) can trigger the extrinsic apoptosis pathway. Our previous study indicated that connexin32 (Cx32) inhibited streptonigrin-induced intrinsic apoptosis via the epidermal growth factor receptor (EGFR) pathway. However, whether Cx32 can exert effects on the extrinsic apoptosis pathway through EGFR signaling remains unclear. In the present study, we investigated the role of Cx32 in extrinsic apoptosis induced by treatment with TNFα + cycloheximide (CHX) or afatinib in human cervical cancer (CaCx) cells...
September 7, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28881811/akt-can-modulate-the-in-vitro-response-of-hnscc-cells-to-irreversible-egfr-inhibitors
#2
Renato José Silva-Oliveira, Matias Melendez, Olga Martinho, Maicon F Zanon, Luciano de Souza Viana, André Lopes Carvalho, Rui Manuel Reis
Epidermal growth factor receptor (EGFR) is overexpressed in up to 90% of head and neck squamous cell carcinoma (HNSCC) tumors. Cetuximab is the first targeted (anti-EGFR) therapy approved for the treatment of HNSCC patients. However, its efficacy is limited due to primary and secondary resistance, and there is no predict biomarkers of response. New generation of EGFR inhibitors with pan HER targeting and irreversible action, such as afatinib and allitinib, represents a significant therapeutic promise. In this study, we intend to compare the potential cytotoxicity of two anti-EGFR inhibitors (afatinib and allitinib) with cetuximab and to identify potential predictive biomarkers of response in a panel of HNSCC cell lines...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878647/adenocarcinoma-of-the-lung-acquiring-resistance-to-afatinib-by-transformation-to-small-cell-carcinoma-a-case-report
#3
Jun Nishimura, Yosuke Miyamoto, Nobukazu Fujimoto, Taichi Ozeki, Kenji Takada, Michiko Asano, Yasuko Fuchimoto, Sae Wada, Shinji Ozaki, Takumi Kishimoto
A 65-year-old woman visited our hospital due to right chest pain and dyspnea on exertion. Chest radiography revealed decreased permeability of the right lung. Computed tomography demonstrated a huge mass in the right upper lobe and right pleural effusion. Right pleural effusion cytology yielded a diagnosis of adenocarcinoma and was positive for mutation of epidermal growth factor receptor (EGFR; exon 21 L858R). Afatinib was selected for the initial treatment. Multiple tumors regressed remarkably, but then rapidly progressed 3 months later...
May 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28860885/osimertinib-in-the-treatment-of-non-small-cell-lung-cancer-design-development-and-place-in-therapy
#4
REVIEW
Mariacarmela Santarpia, Alessia Liguori, Niki Karachaliou, Maria Gonzalez-Cao, Maria Grazia Daffinà, Alessandro D'Aveni, Grazia Marabello, Giuseppe Altavilla, Rafael Rosell
The discovery of epidermal growth factor receptor (EGFR) mutations and subsequent demonstration of the efficacy of genotype-directed therapies with EGFR tyrosine kinase inhibitors (TKIs) marked the advent of the era of precision medicine for non-small-cell lung cancer (NSCLC). First- and second-generation EGFR TKIs, including erlotinib, gefitinib and afatinib, have consistently shown superior efficacy and better toxicity compared with first-line platinum-based chemotherapy and currently represent the standard of care for EGFR-mutated advanced NSCLC patients...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28854272/overall-survival-in-egfr-mutated-non-small-cell-lung-cancer-patients-treated-with-afatinib-after-egfr-tki-and-resistant-mechanisms-upon-disease-progression
#5
A J van der Wekken, J L Kuiper, A Saber, M M Terpstra, J Wei, T J N Hiltermann, E Thunnissen, D A M Heideman, W Timens, E Schuuring, K Kok, E F Smit, A van den Berg, H J M Groen
PURPOSE: To determine survival in afatinib-treated patients after treatment with first-generation EGFR tyrosine kinase inhibitors (TKIs) and to study resistance mechanisms in afatinib-resistant tumors. METHODS: Characteristics and survival of patients treated with afatinib after resistance to erlotinib or gefitinib in two large Dutch centers were collected. Whole exome sequencing (WES) and pathway analysis was performed on available pre- and post-afatinib tumor biopsies and normal tissue...
2017: PloS One
https://www.readbyqxmd.com/read/28839997/the-efficacy-and-toxicity-of-afatinib-in-advanced-egfr-positive-non-small-cell-lung-cancer-patients-after-failure-of-first-generation-tyrosine-kinase-inhibitors-a-systematic-review-and-meta-analysis
#6
Yaxiong Zhang, Siyu Miao, Fang Wang, Wenfeng Fang, Gang Chen, Xi Chen, Fang Yan, Xiaodan Huang, Manli Wu, Yan Huang, Li Zhang
BACKGROUND: The first generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, have become the standard first-line treatment for non-small-cell lung cancer (NSCLC) patients with EGFR mutation. However, there was no pooled analysis focused on the usage of the second-generation TKI, afatinib, in advanced EGFR-positive NSCLC patients after failure of first generation TKIs. Therefore, a meta-analysis was conducted to solve the above question...
July 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28838400/emergence-of-fgfr3-tacc3-fusions-as-a-potential-by-pass-resistance-mechanism-to-egfr-tyrosine-kinase-inhibitors-in-egfr-mutated-nsclc-patients
#7
Sai-Hong Ignatius Ou, Leora Horn, Marcelo Cruz, Davood Vafai, Christine M Lovly, Allison Spradlin, Michael J Williamson, Ibiayi Dagogo-Jack, Adrienne Johnson, Vincent A Miller, Shirish Gadgeel, Siraj M Ali, Alexa B Schrock
Resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancers (NSCLCs) with activating EGFR mutations generally involve development of acquired secondary or tertiary EGFR mutations, such as T790M or C797S. However, case reports have demonstrated that actionable receptor tyrosine kinase fusions such as EML4-ALK, CCDC6-RET, and FGFR3-TACC3 can potentially confer resistance to EGFR TKIs. We seeked to identify the prevalence of FGFR3-TACC3 fusion transcripts as resistance mechanism to EGFR TKIs...
September 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28838394/molecular-profiling-in-italian-patients-with-advanced-non-small-cell-lung-cancer-an-observational-prospective-study
#8
Elisa Gobbini, Domenico Galetta, Marcello Tiseo, Paolo Graziano, Antonio Rossi, Emilio Bria, Massimo Di Maio, Giulio Rossi, Vanesa Gregorc, Ferdinando Riccardi, Vieri Scotti, Anna Ceribelli, Lucio Buffoni, Angelo Delmonte, Tindara Franchina, Maria Rita Migliorino, Diego Cortinovis, Salvatore Pisconti, Paola Bordi, Annamaria Catino, Evaristo Maiello, Francesca Arizio, Silvia Novello
OBJECTIVES: Molecular profiling of advanced non-small-cell lung cancer (NSCLC) is recommended according to European and Italian guidelines. However, molecular routine assessment remains still heterogeneous. This observational study aimed to take a picture of the real clinical practice in molecular testing and therapeutic choices in advanced Italian NSCLCs. MATERIALS AND METHODS: This study prospectively enrolled newly diagnosed advanced or recurrent NSCLCs referred to 38 Italian centres, from November 2014 to November 2015...
September 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28794650/treating-egfr-mutation-resistance-in-non-small-cell-lung-cancer-role-of-osimertinib
#9
REVIEW
Valentina Mazza, Federico Cappuzzo
The discovery of mutations in EGFR significantly changed the treatment paradigm of patients with EGFR-mutant non-small cell lung cancer (NSCLC), a particular group of patients with different clinical characteristics and outcome to EGFR-wild-type patients. In these patients, the treatment of choice as first-line therapy is first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, or afatinib. Inevitably, after the initial response, all patients become refractory to these drugs...
2017: Application of Clinical Genetics
https://www.readbyqxmd.com/read/28790264/-a-case-of-lung-adenocarcinoma-presenting-with-leptomeningeal-carcinomatosis-successfully-treated-with-afatinib-after-erlotinib-induced-hepatotoxicity
#10
Hiroaki Tanaka, Minehiko Inomata, Ryuji Hayashi, Kazuki Shimokawa, Kotaro Tokui, Seisuke Okazawa, Kenta Kambara, Toru Yamada, Toshiro Miwa, Tatsuhiko Kashii, Hirofumi Konishi, Kazuyuki Tobe
A 65-year-old man was diagnosed with leptomeningeal carcinomatosis based on the findings of cerebrospinal fluid cytology and magnetic resonance imaging(MRI).Treatment with erlotinib and bevacizumab was initiated, and partial improvement in consciousness and MRI findings were obtained.However, it was difficult to continue the treatment because of elevation in levels of liver enzymes and melena.We switched the treatment to afatinib monotherapy, and his consciousness improved immediately.Progression -free survival and overall survival from the initiation of the treatment with afatinib were 7 and 9...
July 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28767414/real-world-experience-of-afatinib-as-a-first-line-therapy-for-advanced-egfr-mutation-positive-lung-adenocarcinoma
#11
Sheng-Kai Liang, Min-Shu Hsieh, Meng-Rui Lee, Li-Ta Keng, Jen-Chung Ko, Jin-Yuan Shih
We evaluated the real-world efficacy and side effects of afatinib as a first-line therapy for advanced EGFR mutation-positive lung adenocarcinoma. The medical records of patients receiving afatinib as a first-line therapy after National Health Insurance reimbursement between May 2014 and January 2016 were reviewed, and information on patient characteristics and treatment courses were collected consecutively. Rebiopsy tissue was collected for EGFR mutation and MET amplification analyses. MET amplification was detected by fluorescence in situ hybridization and immunohistochemistry...
July 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28756224/treatment-with-a-programmed-cell-death-1-specific-antibody-has-little-effect-on-afatinib-and-naphthalene-induced-acute-pneumonitis-in-mice
#12
Naoki Hamada, Toyoshi Yanagihara, Kunihiro Suzuki, Saiko Ogata-Suetsugu, Eiji Harada, Hironori Mikumo, Masako Arimura-Omori, Yoichi Nakanishi
Although several antibodies developed to target programmed cell death-1 (PD-1) and its ligand (PD-L1) have demonstrated great promise for the treatment of non-small cell lung cancer (NSCLC), and other malignancies, these therapeutic antibodies can cause pneumonitis. Furthermore, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-induced pneumonitis was reported after treatment with anti PD-1 antibodies. We previously demonstrated that mice with naphthalene-induced airway epithelial injury developed severe gefitinib-induced pneumonitis through a neutrophil-dependent mechanism...
September 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28751244/cost-effectiveness-analysis-of-afatinib-versus-gefitinib-for-first-line-treatment-of-advanced-egfr-mutated-advanced-non-small-cell-lung-cancers
#13
Christos Chouaid, Laura Luciani, Katell LeLay, Pascal Do, Jaafar Bennouna, Maurice Perol, Denis Moro-Sibilot, Alain Vergnenegre, Gérard de Pouvourville
INTRODUCTION: The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib were compared in the multicenter, international, randomized, head-to-head phase 2b LUX-Lung 7 trial for first-line treatment of advanced EGFR mutation-positive NSCLCs. Afatinib and gefitinib costs and patients' outcomes in France were assessed. METHODS: A partitioned survival model was designed to assess the cost-effectiveness of afatinib versus gefitinib for EGFR mutation-positive NSCLCs...
July 24, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28748401/system-biology-approach-to-identify-potential-receptor-for-targeting-cancer-and-biomolecular-interaction-studies-of-indole-2-1-a-isoquinoline-derivative-as-anticancerous-drug-candidate-against-it
#14
Devender Arora, Ritu Chaudhary, Ajeet Singh
Cancer is a public health concern which is spreading throughout the world. Different approaches have been employed to combat this disease. System biology approach has been used to understand the molecular mechanisms of drugs targeting cancer cell's receptor which have opened-up a window to develop effective drugs for it. We have demonstrated biomolecular interaction studies using the rational drug design of indole[2,1-a]isoquinoline derivative as a potent inhibitor against identified cancerous protein PIK3CA -a catalytic sub-unit of PI3K family protein-and compared its affinity with FDA approved drugs for receptors such as dactolisib, idelalisib, and several others such afatinib, avastin, ceritinib and crizotinib, etc...
July 26, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/28747773/deciphering-mechanisms-of-acquired-t790m-mutation-after-egfr-inhibitors-for-nsclc-by-computational-simulations
#15
Bin Zou, Victor H F Lee, Lijiang Chen, Lichun Ma, Debby D Wang, Hong Yan
Metastatic non-small-cell lung cancer (NSCLC) with activating EGFR mutations responds very well to first and second generation tyrosine-kinase inhibitors (TKI) including gefitinib, erlotinib and afatinib. Unfortunately, drug resistance will eventually develop and about half of the cases are secondary to the emergence of acquired T790M somatic mutation. In this work, we prospectively recruited 68 patients with metastatic EGFR-mutated NSCLC who have developed progressive disease after first-line TKI with or without subsequent TKI and/or other systemic therapy...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747569/acquisition-of-the-t790m-resistance-mutation-during-afatinib-treatment-in-egfr-tyrosine-kinase-inhibitor-na%C3%A3-ve-patients-with-non-small-cell-lung-cancer-harboring-egfr-mutations
#16
Kentaro Tanaka, Kaname Nosaki, Kohei Otsubo, Koichi Azuma, Shinya Sakata, Hiroshi Ouchi, Ryotaro Morinaga, Hiroshi Wataya, Akiko Fujii, Noriaki Nakagaki, Nobuko Tsuruta, Masafumi Takeshita, Eiji Iwama, Taishi Harada, Yoichi Nakanishi, Isamu Okamoto
The T790M secondary mutation of the epidermal growth factor receptor (EGFR) gene accounts for 50% to 60% of cases of resistance to the first-generation EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. The prevalence of T790M in EGFR mutation-positive patients who acquire resistance to the irreversible, second-generation EGFR-TKI afatinib has remained unclear, however. We here determined the frequency of T790M acquisition at diagnosis of progressive disease in patients with EGFR-mutated non-small cell lung cancer (NSCLC) treated with afatinib as first-line EGFR-TKI...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28747551/egfr-or-her2-inhibition-modulates-the-tumor-microenvironment-by-suppression-of-pd-l1-and-cytokines-release
#17
Koung Jin Suh, Ji Hea Sung, Jin Won Kim, Song-Hee Han, Hye Seung Lee, Ahrum Min, Mi Hyun Kang, Ji Eun Kim, Ji-Won Kim, Se Hyun Kim, Jeong-Ok Lee, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Seock-Ah Im, Jong Seok Lee
BACKGROUND: Characteristics of tumor microenvironment have been suggested as predictive markers of anti-EGFR or anti-HER2 treatment response. However, the effect of EGFR/HER2 signal blockade on the tumor immune microenvironment is unclear. METHODS: EGFR/HER2 pathway signaling and PD-L1 expression in gastric cancer cell lines were screened by western blot analysis. PD-L1 and HER2 expressions in 251 resected gastric tumors were determined by immunohistochemistry, and changes in EFGR, HER2, and PD-L1 expression in paired specimens between pre- and post-chemotherapy were evaluated...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28742280/clinical-outcomes-in-patients-with-advanced-egfr-mutated-non-small-cell-lung-cancer-in-south-western-sydney-local-health-district
#18
P N Ding, T L Roberts, W Chua, T M Becker, J Descallar, P Y Yip, V J Bray
AIMS: We aim to describe clinical characteristics, treatment patterns and factors influencing outcomes in patients with EGFR-mutated non-small cell lung cancer (NSCLC) in SWSLHD. METHODS: Retrospective review of patients with EGFR-mutated NSCLC diagnosed between January 2010 and June 2016. RESULTS: A total of 85 EGFR-mutated NSCLC patients were identified; 80 (94%) received first line treatment with EGFR-TKI. The median follow-up was 10.7 months with a median duration of treatment of 9 months...
July 25, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28739703/cerebrospinal-fluid-penetration-rate-and-efficacy-of-afatinib-in-patients-with-egfr-mutation-positive-non-small-cell-lung-cancer-with-leptomeningeal-carcinomatosis-a-multicenter-prospective-study
#19
MULTICENTER STUDY
Akihiro Tamiya, Motohiro Tamiya, Takashi Nishihara, Takayuki Shiroyama, Keiko Nakao, Taisuke Tsuji, Naoko Takeuchi, Shun-Ichi Isa, Naoki Omachi, Norio Okamoto, Hidekazu Suzuki, Kyoichi Okishio, Ayano Iwazaki, Kimie Imai, Tomonori Hirashima, Shinji Atagi
BACKGROUND: Afatinib is an effective first-line treatment for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC). However, few reports have addressed the influence of cerebrospinal fluid (CSF) penetration rate on the efficacy of afatinib in patients with central nervous system metastases. Therefore, we conducted a prospective multicenter trial to evaluate the CSF penetration rate and efficacy of afatinib in patients with EGFR mutation-positive NSCLC with leptomeningeal carcinomatosis...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28735814/tyrosine-kinase-inhibitors-as-modulators-of-trastuzumab-mediated-antibody-dependent-cell-mediated-cytotoxicity-in-breast-cancer-cell-lines
#20
Denis M Collins, Kathy Gately, Clare Hughes, Connla Edwards, Anthony Davies, Stephen F Madden, Kenneth J O'Byrne, Norma O'Donovan, John Crown
BACKGROUND: Trastuzumab is an anti-HER2 monoclonal antibody (mAb) therapy capable of antibody-dependent cell-mediated cytotoxicity (ADCC) and used in the treatment of HER2+ breast cancer. Through interactions with FcƴR+ immune cell subsets, trastuzumab functions as a passive immunotherapy. The EGFR/HER2-targeting tyrosine kinase inhibitor (TKI) lapatinib and the next generation TKIs afatinib and neratinib, can alter HER2 levels, potentially modulating the ADCC response to trastuzumab...
July 15, 2017: Cellular Immunology
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