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Erlotinib AND cancer

Ou Yamaguchi, Kyoichi Kaira, Atsuto Mouri, Ayako Shiono, Kosuke Hashimoto, Yu Miura, Fuyumi Nishihara, Yoshitake Murayama, Kunihiko Kobayashi, Hiroshi Kagamu
BACKGROUND: Re-challenge of erlotinib after gefitinib failure is reported to yield some benefit in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation. However, little is known about the re-challenge of afatinib after 1st generate on EGFR tyrosine kinase inhibitor (TKI) failure. METHODS: From May 2015 to August 2018, 62 patients with advanced NSCLC harboring sensitive EGFR mutation received afatinib after gefitinib and/or erlotinib failure at our institution was included in our retrospective study...
February 13, 2019: Cancer Chemotherapy and Pharmacology
Mahmoud S Abdelbaset, Mohamed Abdel-Aziz, Mohamed Ramadan, Mostafa H Abdelrahman, Syed Nasir Abbas Bukhari, Taha F S Ali, Gamal El-Din A Abuo-Rahma
Novel thienoquinoline carboxamide-chalcone derivatives were prepared via the cyclization of acylated chalcones and 2-mercaptoquinoline-3-carbaldehyde in DMF with K2 CO3 . Thienoquinolines 9a-f, h exhibited promising antiproliferative effect against all the tested cell lines and gave a significant activity as EGFR inhibitors, with IC50 values ranging from 0.5 and 3.2 µM, and compounds 9e and 9f being the most active of the series. They also showed better activity than Erlotinib against melanoma cancer cell line A375...
February 5, 2019: Bioorganic & Medicinal Chemistry
Lynn Symonds, Hannah Linden, Vijayakrishna Gadi, Larissa Korde, Eve Rodler, Julie Gralow, Mary Redman, Kelsey Baker, Quan Vicky Wu, Isaac Jenkins, Brenda Kurland, Mitchell Garrison, Julie Smith, Jeanne Anderson, Carol Van Haelst, Jennifer Specht
INTRODUCTION: Angiogenesis and epidermal growth factor receptor signaling are potential therapeutic targets in triple negative breast cancer (TNBC). We hypothesized that targeting these critical pathways would prolong progression-free survival with first-line therapy for metastatic TNBC. PATIENTS AND METHODS: We conducted a phase II trial of nab-paclitaxel and bevacizumab, followed by maintenance therapy with bevacizumab and erlotinib, for patients with metastatic TNBC...
December 14, 2018: Clinical Breast Cancer
Shawn P Kubli, Christian Bassi, Cecilia Roux, Andrew Wakeham, Christoph Göbl, Wenjing Zhou, Soode Moghadas Jafari, Bryan Snow, Lisa Jones, Luis Palomero, Kelsie L Thu, Luca Cassetta, Daniel Soong, Thorsten Berger, Parameswaran Ramachandran, Shakiba P Baniasadi, Gordon Duncan, Moshit Lindzen, Yosef Yarden, Carmen Herranz, Conxi Lazaro, Mandy F Chu, Jillian Haight, Paul Tinto, Jennifer Silvester, David W Cescon, Anna Petit, Sven Pettersson, Jeffrey W Pollard, Tak W Mak, Miguel A Pujana, Paola Cappello, Chiara Gorrini
Cancer cells have higher reactive oxygen species (ROS) than normal cells, due to genetic and metabolic alterations. An emerging scenario is that cancer cells increase ROS to activate protumorigenic signaling while activating antioxidant pathways to maintain redox homeostasis. Here we show that, in basal-like and BRCA1-related breast cancer (BC), ROS levels correlate with the expression and activity of the transcription factor aryl hydrocarbon receptor (AhR). Mechanistically, ROS triggers AhR nuclear accumulation and activation to promote the transcription of both antioxidant enzymes and the epidermal growth factor receptor (EGFR) ligand, amphiregulin (AREG)...
February 7, 2019: Proceedings of the National Academy of Sciences of the United States of America
Tao Shen, Xianshuo Cheng, Cuifeng Xia, Qiang Li, Yi Gao, Dingguo Pan, Xuan Zhang, Ce Zhang, Yunfeng Li
The distal metastasis is the main cause of death in patients with colon cancer. Tyrosine receptor kinase B (TrkB) and ERK signals may be the potential targets for the treatment of colon cancer metastasis. This study aims to investigate whether erlotinib inhibits distant metastasis of colon cancer by regulating TrkB and ERK signaling pathway. Human colon adenocarcinoma cell lines (SW480 and Caco-2) pretreated with exogenous C-X-C motif chemokine ligand 8 (CXCL8) were used to assess the suppressive effect of erlotinib on tumor metastasis, including anoikis, epithelial-mesenchymal transformation (EMT), migration, and invasion...
February 5, 2019: Journal of Cellular Biochemistry
Mingtong Ye, Nengzhi Pang, Ting Wan, Yuanling Huang, Tianyi Wei, Xuye Jiang, Yujia Zhou, Yufeng Huang, Hainan Yang, Zhenfeng Zhang, Lili Yang
Switching aerobic respiration to anaerobic glycolysis of cancer cells plays an important role in development and progression of acquired resistance. Since vitamin C enabled the inhibition of glycolysis of cancer cells, and erlotinib-resistant sub-line of HCC827 (ER6 cells) switched its metabolic features to higher glycolysis for survival, we hypothesize that vitamin C is able to inhibit glycolysis of ER6 cells. In this study, we found that both reduced vitamin C and oxidized vitamin C (DHA) could selectively suppress the viability of ER6 cells...
2019: Journal of Cancer
Koichi Saruwatari, Tokunori Ikeda, Sho Saeki, Naoki Shingu, Kosuke Imamura, Taiyou Komatu, Sunao Ushijima, Hirotaka Maruyama, Kosuke Kashiwabara, Yusuke Tomita, Hidenori Ichiyasu, Kazuhiko Fujii, Takuro Sakagami
BACKGROUND/AIM: The optimal treatment strategy for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) has not yet been fully determined. The aim of this study was to investigate the optimal management of EGFR-mutant NSCLC patients with BM. PATIENTS AND METHODS: A multicenter retrospective study was performed on the clinical outcomes of 81 advanced/recurrent EGFR-mutant NSCLC patients with BM treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) (gefitinib n=52 or erlotinib n=29)...
February 2019: Anticancer Research
Fahim Faruque, Heejung Noh, Arif Hussain, Edward Neuberger, Eberechukwu Onukwugha
BACKGROUND: Pharmacogenetic testing can provide predictive insights about the efficacy and safety of drugs used in cancer treatment. Although many drug-gene associations have been reported in the literature, the strength of evidence supporting each association can vary significantly. Even among the subgroup of drugs classified by the PharmGKB database to have a high or moderate level of evidence, there is limited information regarding the economic value of pharmacogenetic testing. OBJECTIVES: To: (a) summarize the available pharmacoeconomic evidence assessing the value of pharmacogenetic testing for cancer drugs with clinically relevant drug-gene associations; (b) determine the quality of the studies that contain this evidence; and (c) discuss the quality of this evidence with respect to the level of evidence of the drug-gene associations...
February 2019: Journal of Managed Care & Specialty Pharmacy
Alexander Traxl, Severin Mairinger, Thomas Filip, Michael Sauberer, Johann Stanek, Stefan Poschner, Walter Jäger, Viktoria Zoufal, Gaia Novarino, Nicolas Tournier, Martin Bauer, Thomas Wanek, Oliver Langer
P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) are two efflux transporters at the blood-brain barrier (BBB), which effectively restrict brain distribution of diverse drugs, such as tyrosine kinase inhibitors. There is a crucial need for pharmacological ABCB1 and ABCG2 inhibition protocols for a more effective treatment of brain diseases. In the present study, seven marketed drugs (osimertinib, erlotinib, nilotinib, imatinib, lapatinib, pazopanib and cyclosporine A) and one non-marketed drug (tariquidar), with known in vitro ABCB1/ABCG2 inhibitory properties, were screened for their inhibitory potency at the BBB in vivo...
January 29, 2019: Molecular Pharmaceutics
Jui-Feng Hsu, Yen-Lung Lee, Hsu-Liang Chang, Po-Ju Wei, Yu-Ting Shen, Chi-Min Lin, Ching-Yi Li, Inn-Wen Chong, Chih-Jen Yang
PURPOSE: Lung cancer with malignant peritoneal carcinomatosis and malignant ascites is rare, often indicates the terminal stage, and is refractory to treatment. The median survival time of lung cancer patients with malignant ascites has been reported to be as short as 15 days to 2 months in retrospective studies. METHODS: We reviewed all lung cancer patients who had cytologically or pathologically proven malignant ascites and received aggressive therapy including chemotherapy, anti-angiogenesis agents and target therapy at a Taiwan hospital from January 2015 to December 2017...
January 29, 2019: Asia-Pacific Journal of Clinical Oncology
Yuping Liu, Xiangliang Jiang, Yue Gu, Yan Chen
Cutaneous toxicities are the commonest side effects in patients with cancer treated using epidermal growth factor receptor inhibitors such as erlotinib. For patients with such toxicities, there is a lack of safe, effective pharmacological agents. Here we established a skin toxicity model and investigated the preventive and therapeutic effect of Diallyl Trisulfide (DATS) in vivo. The mouse skin toxicities model was established through continuous administration of erlotinib for 49 days. Meanwhile, the mice in the experimental group underwent DATS treatment for 49 days...
January 22, 2019: International Immunopharmacology
Tatsu Matsuzaki, Eri Iwami, Kotaro Sasahara, Aoi Kuroda, Takahiro Nakajima, Takeshi Terashima
RATIONALE: This is the first known report in the English literature to describe a case of metastatic non-small cell lung cancer that has been controlled for >11 years. PATIENT CONCERNS: A 71-year-old man visited our hospital because of dry cough. DIAGNOSIS: Chest computed tomography revealed a tumor on the left lower lobe with pleural effusion, and thoracic puncture cytology indicated lung adenocarcinoma. INTERVENTIONS: Four cycles of carboplatin and docetaxel chemotherapy reduced the size of the tumor; however, it increased in size after 8 months, and re-challenge chemotherapy (RC) with the same drugs was performed...
January 2019: Medicine (Baltimore)
Takuya Shintani, Kazuma Higashisaka, Makiko Maeda, Masaya Hamada, Ryosuke Tsuji, Koudai Kurihara, Yuri Kashiwagi, Atsuhiro Sato, Masanori Obana, Ayaha Yamamoto, Keisuke Kawasaki, Ying Lin, Takashi Kijima, Yuhei Kinehara, Yoshihiro Miwa, Shinichiro Maeda, Eiichi Morii, Atsushi Kumanogoh, Yasuo Tsutsumi, Izumi Nagatomo, Yasushi Fujio
The acquisition of resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) is one of the major problems in the pharmacotherapy against non-small cell lung cancers; however, molecular mechanisms remain to be fully elucidated. Here, using a newly-established erlotinib-resistant cell line, PC9/ER, from PC9 lung cancer cells, we demonstrated that the expression of translation-related molecules, including eukaryotic translation initiation factor 3 subunit C (eIF3c), was upregulated in PC9/ER cells by proteome analyses...
December 25, 2018: Oncotarget
Gyula László Fekete, László Fekete
Erlotinib is a targeted anticancer therapy used for treating epidermal growth factor receptor (EGFR) mutation positive lung cancer in advanced stage as well as for other malignancies. The most common cutaneous side effect of erlotinib, are well documented; however the number of reports regarding cutaneous leukocytoclastic vasculitis (CLCV) are limited. We report a case, a 58-year-old, 60 kg weight, non-smoking woman suffering of lung adenocarcinoma and brain metastases treated with erlotinib monotherapy with 150 mg/day dose, who presents cutaneous leukocytoclastic vasculitis after 8 months of initiating the treatment...
February 2019: Experimental and Therapeutic Medicine
Jieun Park, Yong-Hee Cho, Wook-Jin Shin, Sang-Kyu Lee, JaeHeon Lee, Taehyung Kim, Pu-Hyeon Cha, Jee Sun Yang, Jaebeom Cho, Do Sik Min, Gyoonhee Han, Ho-Young Lee, Kang-Yell Choi
The epidermal growth factor receptor (EGFR) inhibitors such as erlotinib and gefitinib are widely used for treatment of non-small cell lung cancer (NSCLC), but they have shown limited efficacy in an unselected population of patients. The KRAS mutations, which are identified in approximately 20% of NSCLC patients, have shown to be associated with the resistance to the EGFR tyrosine kinase inhibitors (TKIs). Currently, there is no clinically available targeted therapy which can effectively inhibit NSCLC tumors harboring KRAS mutations...
January 24, 2019: Scientific Reports
Thorvardur R Halfdanarson, Nathan R Foster, George P Kim, Jeffrey P Meyers, Thomas C Smyrk, Ann E McCullough, Matthew M Ames, Jeffrry P Jaffe, Steven R Alberts
LESSONS LEARNED: Dual epidermal growth factor receptor (EGFR)-directed therapy with erlotinib and panitumumab in combination with gemcitabine was superior to gemcitabine and erlotinib, but the clinical relevance is uncertain given the limited role of gemcitabine monotherapy.A significantly longer overall survival was observed in patients receiving the dual EGFR-directed therapy.The dual EGFR-directed therapy resulted in increased toxicity. BACKGROUND: Gemcitabine is active in patients with advanced pancreatic adenocarcinoma...
January 24, 2019: Oncologist
Michèle Beau-Faller, Matthieu Texier, Hélène Blons, Nicolas Richard, Fabienne Escande, Samia Melaabi, Sarab Lizard, Florence De Fraipont, Elisabeth Longchampt, Franck Morin, Gérard Zalcman, Jean-Pierre Pignon, Jacques Cadranel
INTRODUCTION: Evaluation of EGFR Mutation status for the administration of EGFR-TKIs in non-small cell lung Carcinoma (ERMETIC) was a prospective study designed to validate the prognostic value of EGFR/KRAS mutations in patients with advanced non-small-cell lung cancer (NSCLC), all receiving a first-generation tyrosine kinase inhibitor, erlotinib. ERMETIC2 was an ancillary project evaluating the clinical value of common EGFR/KRAS-mutated subclones regarding prognosis using highly sensitive molecular detection methods...
December 19, 2018: Clinical Lung Cancer
Lehe Yang, Shichong Lin, Yanting Kang, Youqun Xiang, Lingyuan Xu, Jifa Li, Xuanxuan Dai, Guang Liang, Xiaoying Huang, Chengguang Zhao
BACKGROUND: Rhein is a lipophilic anthraquinone extensively found in medicinal herbs. Emerging evidence suggests that rhein has significant antitumor effects, supporting its potential use as an antitumor agent. The IL6/STAT3 signaling pathway has been suggested as an attractive target for the discovery of novel cancer therapeutics. METHODS: The human pancreatic cancer cell lines AsPC-1, Patu8988T, BxPC-3 and PANC-1, and immunodeficient mice were chosen as models to study the effects of rhein...
January 23, 2019: Journal of Experimental & Clinical Cancer Research: CR
Liliana Belgioia, Isacco Desideri, Angelo Errico, Ciro Franzese, Antonino Daidone, Lorenza Marino, Michele Fiore, Paolo Borghetti, Daniela Greto, Alba Fiorentino
PURPOSE: Aim of the present review is to assess present data about the use of the association of Radiotherapy (RT) and targeted therapy/immunotherapy (TT/IT) in elderly people. DESIGN: PubMed database was searched for English literature published up to December 2017 using the keywords "radiotherapy" combined with "bevacizumab", "cetuximab", "trastuzumab", "erlotinib", "gefitinib", "sorafenib", "sunitinib", "vismodegib", "sonidegib", "ipilimumab", "pembrolizumab", "nivolumab"...
January 2019: Critical Reviews in Oncology/hematology
David Planchard, Michael J Boyer, Jong-Seok Lee, Arunee Dechaphunkul, Parneet K Cheema, Toshiaki Takahashi, Jhanelle E Gray, Marcello Tiseo, Suresh Ramalingam, Alexander Todd, Astrid McKeown, Yuri Rukazenkov, Yuichiro Ohe
INTRODUCTION: In the phase III FLAURA study, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib significantly improved progression-free survival (PFS) versus standard-of-care (SoC) EGFR-TKI (gefitinib or erlotinib), in patients with previously untreated EGFR (exon 19 deletion or L858R) mutation-positive advanced NSCLC. Interim overall survival data were encouraging but not formally statistically significant at current maturity (25%). Here we report exploratory post-progression outcomes...
January 18, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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