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NSCLC egfr

Hidejiro Torigoe, Hiromasa Yamamoto, Masakiyo Sakaguchi, Chen Youyi, Kei Namba, Hiroki Sato, Kazuhiko Shien, Junichi Soh, Ken Suzawa, Shuta Tomida, Kazunori Tsukuda, Shinichiro Miyoshi, Shinichi Toyooka
Epidermal growth factor receptor (EGFR) is a member of the ErbB (HER) family that is known to play important roles in the pathogenesis of various human cancers. Mutations of the EGFR gene are commonly found as oncogenic driver mutations, and have been targeted for treatment in non-small cell lung cancer (NSCLC). Leucine-rich repeat and immunoglobulin-like domain protein-1 (LRIG1) is a cell-surface protein that is known as a negative regulator of the ErbB (HER) family. In this study, we first confirmed that the expression levels of LRIG1 were much lower in NSCLC than in non-malignant cells or tissues...
March 13, 2018: Carcinogenesis
Yang Chen, Youyou Wang, Lujun Zhao, Ping Wang, Jifeng Sun, Rudi Bao, Chenghai Li, Ningbo Liu
Objective: To investigate the potential of HS-10182, a second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), as a radiosensitizer in non-small cell lung cancer (NSCLC). Methods: Two cell lines of NSCLCs, A549 that possesses wild-type (WT) EGFRs and H1975 that possesses EGFR L858R/T790M double mutations, were treated with HS-10182 at various concentrations, and cell viabilities were determined using the MTS assay. The cells were tested by clonogenic survival assays to identify the radiosensitivity of both groups...
February 2018: Cancer Biology & Medicine
Ramon Andrade De Mello, Carles Escriu, Pedro Castelo-Branco, Paloma Lucena Cabral, Giannis Mountzios, Gilberto de Lima Lopes, Pedro Madureira
Introduction: Tyrosine kinase inhibition of the epidermal growth factor receptor (EGFR) is the standard in the first line treatment of patients with advanced non-small-cell lung cancer (NSCLC) harbouring EGFR activating mutations. Here we aim to discern efficacy and toxicity measures through a meta-analysis of published studies that could aid treatment selection. Materials And Methods: We performed a meta-analysis of the main randomized clinical trials evaluating the currently approved EGFR-TKIs in first-line of treatment of EGFR-positive advanced NSCLC...
February 20, 2018: Oncotarget
Jing Zhu, Ying Xin, Xiaoliang Liu, Ying Wang, Ying Liu
Non-small cell lung cancer (NSCLC) accounts for ~85% of lung cancer cases worldwide. Current guidelines recommend the use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors for patients with NSCLC. The EGF/EGFR signaling pathway has been demonstrated to activate nuclear factor (NF)-κB, which may inhibit tumor necrosis factor (TNF)-α induced cell apoptosis. The aim of the present study was to investigate whether inhibiting the EGF/EGFR signaling pathway sensitizes NSCLC cell lines to TNF-α-induced apoptosis...
April 2018: Experimental and Therapeutic Medicine
Sandrine Loubière, Alexandre Drezet, Michèle Beau-Faller, Denis Moro-Sibilot, Sylvie Friard, Marie Wislez, Hélène Blons, Catherine Daniel, Virginie Westeel, Anne Madroszyk, Hervé Léna, Patrick Merle, Julien Mazières, Gérard Zalcman, Roger Lacave, Martine Antoine, Franck Morin, Pascale Missy, Fabrice Barlesi, Pascal Auquier, Jacques Cadranel
ALK rearrangement and EGFR / KRAS mutations constitute the primary biomarkers tested to provide targeted or nontargeted therapies in advanced nonsmall cell lung cancer (NSCLC) patients. Our objective was to assess the cost-effectiveness of biomarker testing for NSCLC.Between 2013 and 2014, 843 treatment-naive patients were prospectively recruited at 19 French hospitals into a longitudinal observational cohort study. Two testing strategies were compared, i.e. with "at least one biomarker status known" and "at least KRAS status known", in addition to "no biomarker testing" as the reference strategy...
March 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Marina Chiara Garassino, Byoung-Chul Cho, Joo-Hang Kim, Julien Mazières, Johan Vansteenkiste, Hervé Lena, Jesus Corral Jaime, Jhanelle E Gray, John Powderly, Christos Chouaid, Paolo Bidoli, Paul Wheatley-Price, Keunchil Park, Ross A Soo, Yifan Huang, Catherine Wadsworth, Phillip A Dennis, Naiyer A Rizvi
BACKGROUND: Immune checkpoint inhibitors are a new standard of care for patients with advanced non-small-cell lung cancer (NSCLC) without EGFR tyrosine kinase or anaplastic lymphoma kinase (ALK) genetic aberrations (EGFR-/ALK-), but clinical benefit in patients with EGFR mutations or ALK rearrangements (EGFR+/ALK+) has not been shown. We assessed the effect of durvalumab (anti-PD-L1) treatment in three cohorts of patients with NSCLC defined by EGFR/ALK status and tumour expression of PD-L1...
March 12, 2018: Lancet Oncology
Yuta Takashima, Jun Sakakibara-Konishi, Yutaka Hatanaka, Kanako C Hatanaka, Yoshihito Ohhara, Satoshi Oizumi, Yasuhiro Hida, Kichizo Kaga, Ichiro Kinoshita, Hirotoshi Dosaka-Akita, Yoshihiro Matsuno, Masaharu Nishimura
BACKGROUND: Approximately 20% to 30% of non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-activating mutations are not responsive to EGFR tyrosine kinase inhibitors (TKIs). Although primary resistance to EGFR-TKIs has been attributed to various genetic alterations, little is known about the clinical and immunopathologic features of patients with primary resistance. The tumor immune microenvironment, including tumor-infiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1), has been reported to play an important role in tumor progression in those with NSCLC...
February 19, 2018: Clinical Lung Cancer
Vincent Plagnol, Samuel Woodhouse, Karen Howarth, Stefanie Lensing, Matt Smith, Michael Epstein, Mikidache Madi, Sarah Smalley, Catherine Leroy, Jonathan Hinton, Frank de Kievit, Esther Musgrave-Brown, Colin Herd, Katherine Baker-Neblett, Will Brennan, Peter Dimitrov, Nathan Campbell, Clive Morris, Nitzan Rosenfeld, James Clark, Davina Gale, Jamie Platt, John Calaway, Greg Jones, Tim Forshew
Circulating tumor DNA (ctDNA) analysis is being incorporated into cancer care; notably in profiling patients to guide treatment decisions. Responses to targeted therapies have been observed in patients with actionable mutations detected in plasma DNA at variant allele fractions (VAFs) below 0.5%. Highly sensitive methods are therefore required for optimal clinical use. To enable objective assessment of assay performance, detailed analytical validation is required. We developed the InVisionFirst™ assay, an assay based on enhanced tagged amplicon sequencing (eTAm-Seq™) technology to profile 36 genes commonly mutated in non-small cell lung cancer (NSCLC) and other cancer types for actionable genomic alterations in cell-free DNA...
2018: PloS One
Emma D Deeks, Gillian M Keating
Afatinib [Giotrif® (EU); Gilotrif® (USA)] is an orally administered, irreversible inhibitor of the ErbB family of tyrosine kinases that provides an important first-line treatment option for advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations (i.e. EGFRactMUT+ ), and an additional treatment option for squamous NSCLC that has progressed following first-line platinum-based chemotherapy. Relative to gefitinib in the first-line treatment of EGFRactMUT+ advanced lung adenocarcinoma, afatinib prolonged progression-free survival (PFS) and time to treatment failure (TTF), but not overall survival (OS)...
2018: Drugs & Therapy Perspectives: for Rational Drug Selection and Use
James H Suh, Alexa B Schrock, Adrienne Johnson, Doron Lipson, Laurie M Gay, Shakti Ramkissoon, Jo-Anne Vergilio, Julia A Elvin, Abdur Shakir, Peter Ruehlman, Karen L Reckamp, Sai-Hong Ignatius Ou, Jeffrey S Ross, Philip J Stephens, Vincent A Miller, Siraj M Ali
BACKGROUND: In our recent study, of cases positive for epidermal growth factor receptor ( EGFR ) exon 19 deletions using comprehensive genomic profiling (CGP), 17/77 (22%) patients with prior standard of care (SOC) EGFR testing results available were previously negative for exon 19 deletion. Our aim was to compare the detection rates of CGP versus SOC testing for well-characterized sensitizing EGFR point mutations (pm) in our 6,832-patient cohort. MATERIALS AND METHODS: DNA was extracted from 40 microns of formalin-fixed paraffin-embedded sections from 6,832 consecutive cases of non-small cell lung cancer (NSCLC) of various histologies (2012-2015)...
March 14, 2018: Oncologist
Caterina Fumagalli, Davide Vacirca, Alessandra Rappa, Antonio Passaro, Juliana Guarize, Paola Rafaniello Raviele, Filippo de Marinis, Lorenzo Spaggiari, Chiara Casadio, Giuseppe Viale, Massimo Barberis, Elena Guerini-Rocco
BACKGROUND: Molecular profiling of advanced non-small cell lung cancers (NSCLC) is essential to identify patients who may benefit from targeted treatments. In the last years, the number of potentially actionable molecular alterations has rapidly increased. Next-generation sequencing allows for the analysis of multiple genes simultaneously. AIMS: To evaluate the feasibility and the throughput of next-generation sequencing in clinical molecular diagnostics of advanced NSCLC...
March 13, 2018: Journal of Clinical Pathology
Elena Castellanos-Rizaldos, Dominik G Grimm, Vasisht Tadigotla, James Hurley, John Healy, Patricia L Neal, Mia Sher, Raajdeep Venkatesan, Chris Karlovich, Mitch Raponi, Anne K Krug, Mikkel Noerholm, Jihane Tannous, Bakhos A Tannous, Luis E Raez, Johan Skog
PURPOSE: About 60% of non-small cell lung cancer (NSCLC) patients develop resistance to targeted epidermal growth factor receptor (EGFR) inhibitor therapy through the EGFR T790M mutation. Patients with this mutation respond well to third generation tyrosine kinase inhibitors, but obtaining a tissue biopsy to confirm the mutation poses risks and is often not feasible. Liquid biopsies using circulating free tumor DNA (cfDNA) have emerged as a non-invasive option to detect the mutation, however sensitivity is low as many patients have too few detectable copies in circulation...
March 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Alona Zer, Jean Claude Cutz, Harman Sekhon, David M Hwang, Christina Sit, Manjula Maganti, Mike Sung, Matthew Binnie, Anthony Brade, Tae Bong Chung, Suzanne Kamel-Reid, Paul Narinder, Ming S Tsao, Tom Waddell, Gilda da Cunha Santos, Milan Patel, Ron F Carter, Natasha B Leighl
BACKGROUND: Molecular testing in advanced lung cancer is standard in guiding treatment selection. However, population-wide implementation of testing remains a challenge. We developed a knowledge translation intervention to improve understanding among diagnostic specialists about molecular testing and appropriate diagnostic sampling in lung cancer. METHODS: Specialty-specific education programs were developed from existing literature and input from Canadian leaders in lung pathology, respirology, interventional radiology, thoracic surgery, radiation and medical oncology...
March 10, 2018: Journal of Thoracic Oncology
Luca Mazzarella, Alessandro Guida, Giuseppe Curigliano
Epidermal Growth Factor Receptor (EGFR)-dependent signaling plays a crucial role in epithelial cancer biology, and dictated the development of several targeting agents. The mouse-human chimeric antibody Cetuximab was among the first to be developed. After about two decades of clinical research it has gained a significant place in the management of advanced colorectal and head and neck cancers, whereas its development in non small cell lung cancer (NSCLC) has not led to a place in routine clinical practice, because of marginal clinical benefit despite statistically significant Phase III trials...
March 14, 2018: Expert Opinion on Biological Therapy
Z Qi, B Zhang, J Zhang, Q Hu, F Xu, B Chen, C Zhu
Lung cancer, especially non-small cell lung cancer (NSCLC), is the leading cause of cancer-related mortality in the world. Both microRNAs and epidermal growth factor receptor (EGFR) are important factors in NSCLC. In our study, the expression of miR-30b in 47 tumor tissues and paired normal tissues of NSCLC were detected by RT-PCR, and we found that miR-30b was down-regulated in NSCLC tumor tissues and was associated with TNM stage, differentiation, and lymph node metastases. Then we investigated the ability of miR-30b to regulate EGFR in several NSCLC cell lines, and found that miR-30b inhibited proliferation, migration and invasion, induced apoptosis and enhanced sensitivity of the NSCLC cells to EGFR tyrosine kinase inhibitors (EGFR-TKIs) by targeting EGFR and repressing EGFR signaling pathways...
2018: Neoplasma
Zhang Zhang, Jian Zou, Lei Yu, Jinfeng Luo, Yan Li, Zhengchao Tu, Xiaomei Ren, Hongcheng Wei, Liyan Song, Xiaoyun Lu, Ke Ding
YL143 was identified as a novel wild-type sparing EGFRT790M inhibitor with good pharmacokinetic properties. It potently suppresses EGFRL858R/T790M with an 50% inhibitory concentration (IC50 ) value of 2.0 ± 0.3 nmol/L, but is approximately 92-folds less potent against EGFRWT kinase. YL143 suppresses cellular proliferation and induces G0/G1 phase arrest and apoptosis in H1975 cells with EGFRL858R/T790M mutation at 30 nmol/L. It also exhibits acceptable pharmacokinetics (PK) parameters with an oral bioavailability value of 25...
March 13, 2018: Cancer Medicine
Malinda Itchins, Stephen Clarke, Nick Pavlakis
No abstract text is available yet for this article.
February 2018: Translational Lung Cancer Research
Fausto Petrelli, Mariangela Maltese, Gianluca Tomasello, Barbara Conti, Karen Borgonovo, Mary Cabiddu, Mara Ghilardi, Michele Ghidini, Rodolfo Passalacqua, Sandro Barni, Matteo Brighenti
Clinicopathologic and molecular characteristics of non-small-cell lung cancers (NSCLCs) associated with a strong expression of programmed death ligand 1 (PD-L1+ in > 5% of cells) have not been well elucidated. Expression of PD-L1 is a poor prognostic factor, but NSCLCs with higher levels of PD-L1 have greater benefit when treated with immunotherapy. We have performed a systematic review to synthesize the available evidence regarding clinicopathologic and molecular variables associated with PD-L1 expression in NSCLC...
February 21, 2018: Clinical Lung Cancer
Sabrina Rossi, Vincenzo Di Noia, Laura Tonetti, Antonia Strippoli, Michele Basso, Giovanni Schinzari, Alessandra Cassano, Antonio Leone, Carlo Barone, Ettore D'Argento
AIM: To evaluate gefitinib outcomes in EGFR-mutated non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations, according to their sarcopenia status. PATIENTS & METHODS: We retrospectively evaluated 33 patients with advanced NSCLC and EGFR mutations (exon 19 or 21), dividing them into sarcopenic patients, with low skeletal muscle index ≤39 cm2 /m2 for women and ≤55 cm2 /m2 for men, and nonsarcopenic patients. RESULTS: Sarcopenia does not affect response to gefitinib treatment in EGFR mutated NSCLC patients, even if it is a bad prognostic indicator for overall survival (p = 0...
March 12, 2018: Future Oncology
Seung Sook Paik, In Kyoung Hwang, Myung Jae Park, Seung Hyeun Lee
BACKGROUND: Although targeted therapy and immuno-oncology have shifted the treatment paradigm for lung cancer, platinum-based combination is still the standard of care for advanced non-small cell lung cancer (NSCLC). Pemetrexed continuation maintenance therapy has been approved and increasingly used for patients with nonsquamous NSCLC. However, the efficacy of this strategy has not been proven in patients without driving mutations. The objective of this study was to compare the clinical benefit of pemetrexed continuation maintenance to conventional platinum-based doublet in epidermal growth factor receptor (EGFR)-negative lung adenocarcinoma...
March 7, 2018: Tuberculosis and Respiratory Diseases
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