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https://www.readbyqxmd.com/read/28546756/new-developments-in-the-treatment-of-advanced-squamous-cell-lung-cancer-focus-on-afatinib
#1
REVIEW
Vera Hirsh
Until recently, few treatment options existed for the treatment of squamous cell carcinoma (SqCC) of the lung, especially in the second-line setting following platinum-based chemotherapy. Accordingly, outcomes in this subtype of non-small-cell lung cancer (NSCLC) were generally poor. In this context, the recent availability of the checkpoint inhibitors nivolumab and pembrolizumab, the anti-VEGFR2 antibody ramucirumab (combined with docetaxel), and the ErbB-family blocker afatinib for the treatment of relapsed/refractory SqCC of the lung represent major advances...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28540585/antibiofilm-activity-and-mode-of-action-of-dmso-alone-and-its-combination-with-afatinib-against-gram-negative-pathogens
#2
Mohd Fakharul Zaman Raja Yahya, Zazali Alias, Saiful Anuar Karsani
Biofilms are complex microbial communities that tend to attach to either biotic or abiotic surface. Enclosed in a self-produced extracellular polymeric substance (EPS) matrix, the biofilms often cause persistent infections. The objective of this study was to investigate the antibiofilm activity of dimethyl sulfoxide (DMSO) and afatinib against Gram-negative pathogens. Test microorganisms used in this study were Escherichia coli ATCC 1299, Pseudomonas aeruginosa ATCC 10145, and Salmonella typhimurium ATCC 14028...
May 24, 2017: Folia Microbiologica
https://www.readbyqxmd.com/read/28540256/concurrent-afatinib-and-whole-brain-radiotherapy-in-exon-19-del-egfr-mutant-lung-adenocarcinoma-a-case-report-and-mini-review-of-the-literature
#3
Chukwuka Eze, Nina-Sophie Hegemann, Olarn Roengvoraphoj, Maurice Dantes, Farkhad Manapov
Leptomeningeal metastases (LM) are found in approximately 3.8% of non-small cell lung cancer cases with an increased incidence in adenocarcinoma, and approximately one-third of patients will present with concomitant brain metastases. We report the case of a 50-year-old male patient with stage IV exon 19-del-EGFR mutant lung adenocarcinoma who progressed on second-generation TKI therapy with manifestation of symptomatic simultaneous diffuse brain and LM. Whole-brain radiotherapy with concurrent afatinib resulted in an almost complete regression of neurological symptoms as well as good, durable radiological response...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28538945/purpuric-drug-eruptions-caused-by-epidermal-growth-factor-receptor-inhibitors-for-non-small-cell-lung-cancer-a-clinicopathologic-study-of-32-cases
#4
Yung-Tsu Cho, Kai-Lung Chen, Yi-Shuan Sheen, Che-Wen Yang, Jau-Yu Liau, Yu-Pin Cheng, Chia-Yu Chu
Importance: Purpuric skin lesions have only rarely been reported in patients receiving epidermal growth factor receptor inhibitors. However, their clinical and histopathologic presentations have varied considerably. Objective: To characterize purpuric skin eruptions caused by epidermal growth factor receptor inhibitors. Design, Setting, and Participants: This prospective study enrolled 32 patients who presented to an integrated dermato-oncologic clinic in a tertiary referral medical center with purpuric skin lesions after using epidermal growth factor receptor inhibitors from January 1, 2013, through December 31, 2015...
May 24, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28527899/egfr-mutation-analysis-for-prospective-patient-selection-in-two-phase-ii-registration-studies-of-osimertinib
#5
Suzanne Jenkins, James Chih-Hsin Yang, Pasi A Jänne, Kenneth S Thress, Karen Yu, Rachel Hodge, Susie Weston, Simon Dearden, Sabina Patel, Mireille Cantarini, Frances A Shepherd
INTRODUCTION: Osimertinib is an oral, CNS active, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for the treatment of EGFR T790M-positive advanced non-small cell lung cancer (NSCLC). Here we evaluate EGFR mutation frequencies in two Phase II studies of osimertinib (AURA extension and AURA2). METHODS: Patients with EGFR mutation-positive advanced NSCLC provided tumor samples following progression on their latest line of therapy for mandatory central T790M testing for study selection criteria...
May 17, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28521301/activation-of-signal-transducer-and-activator-of-transcription-3-stat3-signaling-in-egfr-mutant-non-small-cell-lung-cancer-nsclc
#6
Carles Codony-Servat, Jordi Codony-Servat, Niki Karachaliou, Miguel Angel Molina, Imane Chaib, Jose Luis Ramirez, Maria de Los Llanos Gil, Flavio Solca, Trever G Bivona, Rafael Rosell
Gefitinib, erlotinib or afatinib are the current treatment for non-small-cell lung cancer (NSCLC) harboring an activating mutation of the epidermal growth factor receptor (EGFR), but less than 5% of patients achieve a complete response and the median progression-free survival is no longer than 12 months. Early adaptive resistance can occur as soon as two hours after starting treatment by activating signal transducer and activation of transcription 3 (STAT3) signaling. We investigated the activation of STAT3 in a panel of gefitinib-sensitive EGFR mutant cell lines, and gefitinib-resistant PC9 cell lines developed in our laboratory...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28521295/change-from-lung-adenocarcinoma-to-small-cell-lung-cancer-as-a-mechanism-of-resistance-to-afatinib
#7
Paolo Manca, Marco Russano, Francesco Pantano, Giuseppe Tonini, Daniele Santini
We report the case of a patient affected by advanced EGFR mutation-positive lung who experienced resistance to therapy during treatment with Afatinib through the occurrence of a switch of tumor histotype to small cell lung cancer (SCLC) with features of a G3 neuroendocrine carcinoma. Unexpectedly, the switch to SCLC histotype occurred in the only site not responsive to afatinib and subsequently the most responsive to chemotherapy. Our case shows that occurrence of switch to SCLC is a possible mechanism of resistance during treatment with Afatinib...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28513466/non-small-cell-lung-cancer-mutations-targeted-and-combination-therapy
#8
Justyna Kutkowska, Irena Porębska, Andrzej Rapak
Year after year, a growing number of cases of non-small cell lung cancer (NSCLC), mostly caused by smoking, have been noted. Most patients die because of the late detection of cancer and tumor resistance to treatment with cytostatics. Treatment of patients with advanced NSCLC is impeded by the low sensitivity of the tumor to cytostatic agents and the co-existence of many diseases, which substrate is, like lung cancer, cigarette smoking. Along with the development of molecular biology, targeted therapy has started to be used, affecting specific signaling pathways involved in the processes of oncogenesis...
May 17, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28503070/tyrosine-kinase-inhibitor-combination-therapy-in-first-line-treatment-of-non-small-cell-lung-cancer-systematic-review-and-network-meta-analysis
#9
Sarah Batson, Stephen A Mitchell, Ricarda Windisch, Elisabetta Damonte, Veronica C Munk, Noemi Reguart
INTRODUCTION: The introduction of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has improved the outlook for patients with advanced non-small-cell lung cancer (NSCLC) with EGFR+ mutations. However, most patients develop resistance, with the result that median progression-free survival (PFS) iŝ12 months. Combining EGFR-TKIs with other agents, such as bevacizumab, is a promising approach to prolonging remission. This systematic review and network meta-analysis (NMA) were undertaken to assess available evidence regarding the benefits of first-line combination therapy involving EGFR-TKIs in patients with advanced NSCLC...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28502724/durable-response-to-afatinib-in-lung-adenocarcinoma-harboring-nrg1-gene-fusions
#10
Nathan D Gay, Ying Wang, Carol Beadling, Andrea Warrick, Tanaya Neff, Christopher L Corless, Khaled Tolba
No abstract text is available yet for this article.
May 10, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28500237/resistance-to-ret-inhibition-in-ret-rearranged-nsclc-is-mediated-by-reactivation-of-ras-mapk-signaling
#11
Sarah K Nelson-Taylor, Anh T Le, Minjae Yoo, Laura Schubert, Katie M Mishall, Andrea Doak, Marileila Varella-Garcia, Aik-Choon Tan, Robert C Doebele
Oncogenic rearrangements in RET are present in 1-2% of lung adenocarcinoma (LAD) patients. Ponatinib is a multi-kinase inhibitor with low-nanomolar potency against the RET kinase domain. Here, we demonstrate that ponatinib exhibits potent anti-proliferative activity in RET fusion positive LC-2/ad LAD cells and inhibits phosphorylation of the RET fusion protein and signaling through ERK1/2 and AKT. Using distinct dose-escalation strategies, two ponatinib-resistant LC-2/ad cell lines, PR1 and PR2, were derived...
May 12, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28499641/outcomes-of-research-biopsies-in-clinical-trials-of-egfr-mutation-positive-non-small-cell-lung-cancer-patients-pretreated-with-egfr-tyrosine-kinase-inhibitors
#12
Bin-Chi Liao, Ya-Ying Bai, Jih-Hsiang Lee, Chia-Chi Lin, Shu-Yung Lin, Yee-Fan Lee, Chao-Chi Ho, Jin-Yuan Shih, Yeun-Chung Chang, Chong-Jen Yu, James Chih-Hsin Yang, Pan-Chyr Yang
BACKGROUND/PURPOSE: Research biopsies (RBs) are crucial for developing novel molecular targeted agents. However, the safety and diagnostic yields of RBs have not been investigated in EGFR mutation-positive non-small cell lung cancer (NSCLC) patients pretreated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). METHODS: We searched the medical records of NSCLC patients who participated in lung cancer clinical trials and underwent mandatory RBs between 2012 and 2014 at our institution...
May 9, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28487443/her2-reactivation-through-acquisition-of-the-her2-l755s-mutation-as-a-mechanism-of-acquired-resistance-to-her2-targeted-therapy-in-her2-breast-cancer
#13
Xiaowei Xu, Carmine De Angelis, Kathleen A Burke, Agostina Nardone, Huizhong Hu, Lanfang Qin, Jamunarani Veeraraghavan, Vidyalakshmi Sethunath, Laura M Heiser, Nicholas J Wang, Charlotte K Y Ng, Edward Chen, Alexander Renwick, Tao Wang, Sarmistha Nanda, Martin Shea, Tamika Mitchell, Mahitha Rajendran, Ian Waters, Daniel J Zabransky, Kenneth L Scott, Carolina Gutierrez, Chandandeep Nagi, Felipe C Geyer, Gary C Chamness, Ben Ho Park, Chad Shaw, Susan G Hilsenbeck, Mothaffar F Rimawi, Joe W Gray, Britta Weigelt, Jorge S Reis-Filho, C Kent Osborne, Rachel Schiff
Purpose: Resistance to anti-HER2 therapies in HER2+ breast cancer can occur through activation of alternative survival pathways or reactivation of the HER signaling network. Here we employed BT474 parental and treatment-resistant cell line models to investigate a mechanism by which HER2+ breast cancer can reactivate the HER network under potent HER2-targeted therapies. <p>Experimental Design: Resistant derivatives to lapatinib (L), trastuzumab (T), or the combination (LR/TR/LTR) were developed independently from two independent estrogen receptor ER+/HER2+ BT474 cell lines (AZ/ATCC)...
May 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28484248/hydration-effects-on-the-efficacy-of-the-epidermal-growth-factor-receptor-kinase-inhibitor-afatinib
#14
Srinivasaraghavan Kannan, Mohan R Pradhan, Garima Tiwari, Wei-Chong Tan, Balram Chowbay, Eng Huat Tan, Daniel Shao-Weng Tan, Chandra Verma
Small molecules targeting the EGFR tyrosine kinase domain have been used with some success at treating patients with non-small cell lung cancer driven by activating mutations in the kinase domain. The initial class of inhibitors displaced ATP noncovalently but were rendered ineffective due to the development of resistance mutations in the kinase domain. These were overcome by the development of covalent inhibitors such as afatinib which also bind in the ATP pocket. However pooled analysis of two recent clinical trials LUX-3 and LUX-6 demonstrated an unprecedented overall survival benefit of afatinib over chemotherapy for the EGFR (19del) , but not the EGFR (L858R) ...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28469968/the-selective-c-met-inhibitor-tepotinib-can-overcome-epidermal-growth-factor-receptor-inhibitor-resistance-mediated-by-aberrant-c-met-activation-in-nsclc-models
#15
Manja Friese-Hamim, Friedhelm Bladt, Giuseppe Locatelli, Uz Stammberger, Andree Blaukat
Non-small cell lung cancer (NSCLC) sensitive to first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) often acquires resistance through secondary EGFR mutations, including the T790M mutation, aberrant c-Met receptor activity, or both. We assessed the ability of the highly selective c-Met inhibitor tepotinib to overcome EGFR TKI resistance in various xenograft models of NSCLC. In models with EGFR-activating mutations and low c-Met expression (patient explant-derived LU342, cell line PC-9), EGFR TKIs caused tumors to shrink, but growth resumed upon cessation of treatment...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28467720/second-line-therapy-of-squamous-non-small-cell-lung-cancer-an-evolving-landscape
#16
Chiara Lazzari, Niki Karachaliou, Vanesa Gregorc, Alessandra Bulotta, Maria Gonzalez-Cao, Alberto Verlicchi, Giuseppe Altavilla, Rafael Rosell, Mariacarmela Santarpia
The treatment of lung cancer has radically changed over the last few years. The discovery of druggable oncogenic alterations and the introduction of immunotherapy have provided lung cancer patients with the possibility of more efficient and less toxic therapeutic alternatives than chemotherapy. In the case of lung squamous cell carcinoma (LSCC), the treatment progress is slower than adenocarcinoma, for which several targeted agents have been already approved. The standard first-line therapy for LSCC, in most sites of the world, is platinum-based chemotherapy...
May 15, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28464435/management-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-related-cutaneous-and-gastrointestinal-toxicities
#17
REVIEW
Derrick Chen-Wee Aw, Eng Huat Tan, Tan Min Chin, Hong Liang Lim, Haur Yueh Lee, Ross A Soo
Patients with advanced stage non-small cell lung cancer with sensitizing epidermal growth factor receptor (EGFR) mutations using EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib, gefitinib and afatinib as first-line treatment had better progression-free survival, overall response rate and quality of life than those on chemotherapy. Although EGFR TKIs are commonly associated with skin-related (rash, xerosis and paronychia) and gastrointestinal-related (diarrhea and stomatitis) adverse events (AEs), these effects are usually mild...
May 2, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28462807/therapeutic-efficacy-comparison-of-5-major-egfr-tkis-in-advanced-egfr-positive-non-small-cell-lung-cancer-a-network-meta-analysis-based-on-head-to-head-trials
#18
Yaxiong Zhang, Zhonghan Zhang, Xiaodan Huang, Shiyang Kang, Gang Chen, Manli Wu, Siyu Miao, Yan Huang, Hongyun Zhao, Li Zhang
BACKGROUND: Five major first- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), including erlotinib, gefitinib, icotinib, afatinib, and dacomitinib, are currently optional for patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, there was no head-to-head-based network meta-analysis among all the TKIs in EGFR-mutated populations. METHODS: Eligible literature was searched from an electronic database...
October 27, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28450659/recent-management-of-patients-with-advanced-epidermal-growth-factor-receptor-mutation-non-small-cell-lung-cancer-role-of-afatinib-and-lesson-learned-for-developing-countries
#19
Zulkifli Amin, Vito Filbert Jayalie, Wulyo Rajabto
Lung cancer is a devastating disease with a high incidence, mortality and morbidity rate, especially in developing countries. Conventional treatment with cytotoxic chemotherapy has some limitations attributed to chemoresistance and toxicity. Recent advances have shown that first generation Tyrosine Kinase Inhibitor (TKI), Gefitinib and Erlotinib, and the newest available second generation Tyrosine Kinase Inhibitor (TKI), Afatinib, have the potential to be an option in the management of patients with epidermal growth factor receptor/ EGFR mutation positive advanced/ metastatic non-small cell lung cancer...
January 2017: Acta Medica Indonesiana
https://www.readbyqxmd.com/read/28448787/relationship-between-her2-and-jak-stat-socs3-signaling-pathway-and-clinicopathological-features-and-prognosis-of-ovarian-cancer
#20
An-Quan Shang, Jian Wu, Feng Bi, Yu-Jie Zhang, Lei-Rong Xu, Ling-Ling Li, Fei-Fei Chen, Wei-Wei Wang, Jian-Jun Zhu, You-Yi Liu
OBJECTIVE: The study aims to explore the relationship between expressions of HER2 and JAK/STAT3-SOCS3 signaling pathway and clinicopathological features and prognosis of ovarian cancer (OC). METHODS: A total of 136 OC patients were collected. Immunohistochemistry was applied to measure the expressions of STAT3, p-STAT3, SOCS3, HER2 and p-HER2 in the tumor tissues and adjacent normal tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expressions of HER2, SOCS3 and STAT3 and western blotting was applied for protein expressions of HER2, p-HER2, SOCS3, STAT3 and p-STAT3 in the tumor tissues and adjacent normal tissues...
April 27, 2017: Cancer Biology & Therapy
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