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https://www.readbyqxmd.com/read/30506897/the-effects-of-switching-egfr-tki-treatments-for-nonsmall-cell-lung-cancer-because-of-adverse-events
#1
Yoshihiko Sakata, Kodai Kawamura, Naoki Shingu, Shigeo Hiroshige, Yuko Yasuda, Yoshitomo Eguchi, Keisuke Anan, Junpei Hisanaga, Tatsuya Nitawaki, Aiko Nakano, Kazuya Ichikado
BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used to treat patients with nonsmall cell lung cancer (NSCLC) and EGFR driver mutations. Although some patients discontinued these treatments because of adverse events, it is unclear whether switching EGFR-TKI because of adverse events provides a benefit. METHODS: This retrospective study evaluated data from 22 patients with EGFR mutation-positive NSCLC who received at least two EGFR-TKIs that were switched because of adverse events (March 2011 to September 2017)...
December 2, 2018: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/30504427/expression-of-mt4-mmp-egfr-and-rb-in-triple-negative-breast-cancer-strongly-sensitizes-tumors-to-erlotinib-and-palbociclib-combination-therapy
#2
Pierre Foidart, Cassandre Yip, Jean Radermacher, Mehdi Lienard, Silvia Blacher, Laetitia Montero-Ruiz, Erik Maquoi, Elodie Montaudon, Sophie Chateau-Joubert, Joelle Collignon, Michel Coibion, Véronique Jossa, Elisabetta Marangoni, Agnes Noel, Nor Eddine Sounni, Guy Jerusalem
PURPOSE: Here, we investigated the clinical relevance of an unprecedented combination of three biomarkers in triple-negative breast cancer (TNBC), both in human samples and in patient-derived xenografts of TNBC (PDX-TNBC): epidermal growth factor receptor (EGFR), its recently identified partner (MT4-MMP) and retinoblastoma protein (RB). EXPERIMENTAL DESIGN: Immunohistochemistry (IHC) analyses were conducted on human and PDX-TNBC samples to evaluate the production of the three biomarkers...
November 30, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30500458/small-molecule-inhibitors-targeting-the-egfr-erbb-family-of-protein-tyrosine-kinases-in-human-cancers
#3
REVIEW
Robert Roskoski
The EGFR family is among the most investigated receptor protein-tyrosine kinase groups owing to its general role in signal transduction and in oncogenesis. This family consists of four members that belong to the ErbB lineage of proteins (ErbB1-4). The ErbB proteins function as homo and heterodimers. These receptors contain an extracellular domain that consists of four parts: domains I and III are leucine-rich segments that participate in growth factor binding (except for ErbB2) and domains II and IV contain multiple disulfide bonds...
November 27, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30499387/insight-into-binding-mechanisms-of-egfr-allosteric-inhibitors-using-molecular-dynamics-simulations-and-free-energy-calculations
#4
Shanhe Wan, Ruohong Yan, Ying Jiang, Zhonghuang Li, Xiaoyun Wu
Lung cancer is the leading cause of cancer death, and EGFR kinase domain mutations are a common cause of NSCLCs, a major subtype of lung cancers. Patients harboring most of these mutations respond well to the EGFR inhibitors Gefitinib and Erlotinib initially, but soon develop resistance to them due to the emergence of the gatekeeper mutation T790M. The new-generation inhibitors such as AZD9291, HM61713, CO-1686, and WZ4002 can overcome T790M through covalent binding to Cys 797, but ultimately lose their efficacy upon the emergence of the C797S mutation that abolishes the covalent bonding...
November 30, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/30499112/modeling-epidermal-growth-factor-inhibitor-mediated-enhancement-of-photodynamic-therapy-efficacy-using-3d-mesothelioma-cell-culture
#5
Gwendolyn Cramer, Michael Shin, Sarah Hagan, Sharyn Katz, Charles B Simone, Theresa M Busch, Keith A Cengel
We have demonstrated that lung sparing surgery with intraoperative photodynamic therapy (PDT) achieves remarkably extended survival for patients with malignant pleural mesothelioma (MPM). Nevertheless, most patients treated using this approach experience local recurrence, so it is essential to identify ways to enhance tumor response. We previously reported that PDT transiently activates EGFR/STAT3 in lung and ovarian cancer cells and inhibiting EGFR via erlotinib can increase PDT sensitivity. Additionally, we have seen higher EGFR expression associating with worse outcomes after Photofrin-mediated PDT for MPM, and the extensive desmoplastic reaction associated with MPM influences tumor phenotype and therapeutic response...
November 29, 2018: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/30498728/effect-of-erlotinib-plus-bevacizumab-on-brain-metastases-in-patients-with-non-small-cell-lung-cancer
#6
Yasuhiro Chikaishi, Masatoshi Kanayama, Akihiro Taira, Yusuke Nabe, Shinji Shinohara, Taiji Kuwata, Masaru Takenaka, Soichi Oka, Ayako Hirai, Koji Kuroda, Naoko Imanishi, Yoshinobu Ichiki, Fumihiro Tanaka
Background: The standard therapy for brain metastasis (BM) in non-small cell lung cancer (NSCLC) is radiation therapy (RT), although it is associated with complications such as leukoencephalopathy. In the current report, we retrospectively review data from eight patients who had NSCLC and harbored epidermal growth factor receptor (EGFR) mutations, and who were received erlotinib plus bevacizumab (E+B) as first-line therapy for BM. Methods: Patients were given E+B as first therapy for BM until August 2017 at our institution...
October 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/30498720/moving-from-late-to-early-stage-disease-lessons-learned-from-erlotinib-in-pancreatic-cancer
#7
EDITORIAL
Andrew H Ko
No abstract text is available yet for this article.
October 2018: Hepatobiliary Surgery and Nutrition
https://www.readbyqxmd.com/read/30487162/lrig1-acts-as-a-critical-regulator-of-melanoma-cell-invasion-migration-and-vasculogenic-mimicry-upon-hypoxia-by-regulating-egfr-erk-triggered-emt
#8
Wei Li, Yubo Zhou
Intratumoral hypoxia is a well-known feature of solid cancers and constitutes a major contributor to cancer metastasis and poor outcomes including melanoma. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) participates in the aggressive progression of several tumors, where its expression is frequently decreased. In the present study, hypoxia exposure aggravated melanoma cell invasion, migration, vasculogenic mimicry (VM) and epithelial-mesenchymal transition (EMT). During this process, LRIG1 expression was also decreased...
November 28, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/30485439/3d-culture-models-of-malignant-mesothelioma-reveal-a-powerful-interplay-between-photodynamic-therapy-and-kinase-suppression-offering-hope-to-reduce-tumor-recurrence
#9
Bryan Q Spring, David Kessel
In this issue, Cramer et al. introduce 3D culture models of metastatic mesothelioma to investigate basic cancer biology and new combination therapies for combating this complex and lethal disease. The results suggest that erlotinib-enhanced photodynamic therapy (PDT) could further improve the efficacy of intraoperative light-activation to mop up residual tumor deposits in the clinic following surgical removal of macroscopic mesothelioma metastases. This article is protected by copyright. All rights reserved...
November 28, 2018: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/30485437/clinical-outcomes-and-secondary-epidermal-growth-factor-receptor-egfr-t790m-mutation-among-first-line-gefitinib-erlotinib-and-afatinib-treated-non-small-cell-lung-cancer-patients-with-activating-egfr-mutations
#10
Yen-Ting Lin, Jin-Shing Chen, Wei-Yu Liao, Chao-Chi Ho, Chia-Lin Hsu, Ching-Yao Yang, Kuan-Yu Chen, Jih-Hsiang Lee, Zhong-Zhe Lin, Jin-Yuan Shih, James Chih-Hsin Yang, Chong-Jen Yu
Gefitinib, erlotinib and afatinib are approved for first-line treatment of advanced non-small cell lung cancer (NSCLC) bearing an activating epidermal growth factor receptor (EGFR) mutation. However, the clinical outcomes among the three EGFR tyrosine kinase inhibitors (TKIs) are still controversial. We aimed to evaluate clinical outcomes and secondary EGFR T790M mutation among the three EGFR TKIs. From May 2014 to January 2016, a total of 301 patients received treatment with gefitinib, erlotinib or afatinib, for first-line treatment of advanced NSCLC with an activating EGFR mutation, based on their clinicians' choice...
November 28, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/30483119/biodegradable-nanoparticles-mediated-co-delivery-of-erlotinib-eltn-and-fedratinib-fdtn-toward-the-treatment-of-eltn-resistant-non-small-cell-lung-cancer-nsclc-via-suppression-of-the-jak2-stat3-signaling-pathway
#11
Donglai Chen, Fuquan Zhang, Jinhui Wang, Hua He, Shanzhou Duan, Rongying Zhu, Chang Chen, Lichen Yin, Yongbing Chen
Background: Erlotinib (ELTN)-based targeted therapy as first-line treatment for epidermal growth factor receptor (EGFR)-mutant lung cancers suffers from insufficient selectivity, side effects, and drug resistance, which poses critical challenges in the clinical setting. Acquired resistance of ELTN results in extremely poor prognoses of non-small cell lung cancer (NSCLC) patients, wherein activation of the JAK2/STAT3 signaling pathway has been proven to induce acquired ELTN resistance. Methods: In this study, we developed a nanoparticle (NP) delivery system based on Food and Drug Administration (FDA)-approved poly(ethylene glycol) (PEG)-poly(lactic acid) (PLA) for the co-delivery of ELTN and fedratinib (FDTN, a small-molecular, highly selective JAK2 inhibitor)...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/30481646/design-synthesis-and-cytotoxicity-of-chimeric-erlotinib-alkylphospholipid-hybrids
#12
Md Maqusood Alam, Ahmed H E Hassan, Kun Won Lee, Min Chang Cho, Ji Seul Yang, Jiho Song, Kyung Hoon Min, Jongki Hong, Dong-Hyun Kim, Yong Sup Lee
Two series of erlotinib-alkylphospholipid hybrids were prepared and evaluated for their antiproliferative activities against a panel of four cell lines representing lung, breast, liver and skin cancers using erlotinib and miltefosine as reference standards. Amide analogs elicited more enhanced cytotoxic activity than analogous esters. Amide derivatives 8d and 8e exhibited promising broad-spectrum antiproliferative activity and higher efficacy than reference erlotinib and miltefosine. Their cellular GI50 values was in the ranges of 24...
November 19, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/30480362/cd146-mediated-acquisition-of-stemness-phenotype-enhances-tumor-invasion-and-metastasis-after-egfr-tki-resistance-in-lung-cancer
#13
Fan Zhang, Jia Wang, Xiaobo Wang, Nan Wei, Haiyang Liu, Xiaoju Zhang
INTRODUCTION: Tumors are more likely to metastasize after development of resistance to EGFR TKIs. CD146 is a multi-functional molecule and is implicated in tumor invasion and metastasis; however, its role in lung cancer has not been clearly established. OBJECTIVE: Here we aimed to explore the relationship between CD146-pathway and stem cell phenotype after EGFR-TKI resistance in lung cancer. METHODS: EGFR-TKI resistance cell lines were established by exposing parental cells to Erlotinib/Gefitinib...
November 27, 2018: Clinical Respiratory Journal
https://www.readbyqxmd.com/read/30472556/first-line-onartuzumab-plus-erlotinib-treatment-for-patients-with-met-positive-and-egfr-mutation-positive-non-small-cell-lung-cancer
#14
Kazuma Kishi, Hiroshi Sakai, Takashi Seto, Toshiyuki Kozuki, Makoto Nishio, Fumio Imamura, Hiroshi Nokihara, Miyako Satouchi, Shintaro Nakagawa, Takashi Tahata, Kazuhiko Nakagawa
INTRODUCTION: The phase II JO28638 study evaluated first-line onartuzumab plus erlotinib in patients with MET-positive advanced, metastatic, or post-operative recurrent non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The study was stopped following termination of the global METLung study (OAM4971g), which showed lack of efficacy in the onartuzumab/erlotinib arm. We present immature efficacy and safety data from JO28638. MATERIALS AND METHODS: Chemotherapy-naïve patients aged ≥ 20 years were enrolled...
October 31, 2018: Cancer Treatment and Research Communications
https://www.readbyqxmd.com/read/30466406/a-systematic-review-of-non-standard-dosing-of-oral-anticancer-therapies
#15
Faouzi Djebbari, Nicola Stoner, Verna Teresa Lavender
BACKGROUND: The use of oral systemic anticancer therapies (SACT) has increased and led to improved cancer survival outcomes, particularly with the introduction of small molecule targeted agents and immunomodulators. Oral targeted SACT are, however, associated with toxicities, which might result in reduced quality of life and non-adherence. To reduce treatment-related toxicity, the practice of non-standard dosing is increasing; however guidance to govern this practice is limited. A systematic review was conducted to identify evidence of, and outcomes from, non-standard dosing of oral SACT in oncology and malignant haematology...
November 22, 2018: BMC Cancer
https://www.readbyqxmd.com/read/30461012/upregulation-of-transient-receptor-potential-melastatin-6-channel-expression-by-rosiglitazone-and-all-trans-retinoic-acid-in-erlotinib-treated-renal-tubular-epithelial-cells
#16
Aya Manabe, Chisa Furukawa, Hajime Hasegawa, Toshiyuki Matsunaga, Satoshi Endo, Akira Ikari
Anti-epidermal growth factor receptor (EGFR) drugs including erlotinib cause a side effect of hypomagnesemia. In lung adenocarcinoma A549 cells, anticancer agents such as cisplatin and doxorubicin dose-dependently increased toxicity, but the effects were significantly suppressed by culturing the cells in low Mg2+ -containing media. To obtain the maximum effect in cancer chemotherapy, it should be necessary to prevent the reduction of body Mg 2+ content. Anti-EGFR drugs inhibit EGF-induced elevation of transient receptor potential melastatin 6 (TRPM6) Mg 2+ channel in renal tubular epithelial NRK-52E cells...
November 21, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30459935/systematic-review-and-meta-analysis-of-third-line-salvage-therapy-for-the-treatment-of-advanced-non-small-cell-lung-cancer-a-meta-analysis-of-randomized-controlled-trials
#17
Nan Zhang, Nan Guo, Liang Tian, Zhigang Miao
Purpose: We performed a systematic review and meta-analysis to investigate the efficacy of third-line treatment for advanced non-small-cell lung cancer (NSCLC). Materials and Methods: Relevant trials were identified by searching electronic databases and conference meetings. Prospective randomized controlled trials (RCTs) assessing third-line therapy in advanced NSCLC patients were included. Outcomes of interest included overall survival (OS) and progression-free survival (PFS)...
October 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/30445769/mechanism-of-resistance-to-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-and-a-potential-treatment-strategy
#18
REVIEW
Tatsuya Nagano, Motoko Tachihara, Yoshihiro Nishimura
Treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) improves the overall survival of patients with EGFR -mutated non-small-cell lung cancer (NSCLC). First-generation EGFR-TKIs (e.g., gefitinib and erlotinib) or second-generation EGFR-TKIs (e.g., afatinib and dacomitinib) are effective for the treatment of EGFR -mutated NSCLC, especially in patients with EGFR exon 19 deletions or an exon 21 L858R mutation. However, almost all cases experience disease recurrence after 1 to 2 years due to acquired resistance...
November 15, 2018: Cells
https://www.readbyqxmd.com/read/30444685/select-a-phase-ii-trial-of-adjuvant-erlotinib-in-patients-with-resected-epidermal-growth-factor-receptor-mutant-non-small-cell-lung-cancer
#19
Nathan A Pennell, Joel W Neal, Jamie E Chaft, Christopher G Azzoli, Pasi A Jänne, Ramaswamy Govindan, Tracey L Evans, Daniel B Costa, Heather A Wakelee, Rebecca S Heist, Marc A Shapiro, Alona Muzikansky, Sudish Murthy, Michael Lanuti, Valerie W Rusch, Mark G Kris, Lecia V Sequist
PURPOSE: Given the pivotal role of epidermal growth factor receptor (EGFR) inhibitors in advanced EGFR-mutant non-small-cell lung cancer (NSCLC), we tested adjuvant erlotinib in patients with EGFR-mutant early-stage NSCLC. MATERIALS AND METHODS: In this open-label phase II trial, patients with resected stage IA to IIIA (7th edition of the American Joint Committee on Cancer staging system) EGFR-mutant NSCLC were treated with erlotinib 150 mg per day for 2 years after standard adjuvant chemotherapy with or without radiotherapy...
November 16, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/30431091/meta%C3%A2-analysis-of-current-chemotherapy-regimens-in-advanced-pancreatic-cancer-to-prolong-survival-and-reduce-treatment%C3%A2-associated-toxicities
#20
Jie Chen, Linli Chen, Jianping Yu, Yanmei Xu, Xiaohui Wang, Ziqian Zeng, Ning Liu, Fan Xu, Shu Yang
Unresectable advanced pancreatic cancer (APC) is a highly lethal malignancy. Although numerous chemotherapeutic regimens are available, evidence regarding the survival extension, the life quality improvement, the associated risks and occurrence rates of adverse effects, is required. The effects of 19 chemotherapy regimens on survival and treatment‑associated toxicities in the context of APC treatment were comparatively assessed. A total of 23 randomized controlled trials were included in this network meta‑analysis...
November 9, 2018: Molecular Medicine Reports
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