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https://www.readbyqxmd.com/read/29666949/precision-medicine-against-alk-positive-non-small-cell-lung-cancer-beyond-crizotinib
#1
REVIEW
Biagio Ricciuti, Andrea De Giglio, Carmen Mecca, Cataldo Arcuri, Sabrina Marini, Giulio Metro, Sara Baglivo, Angelo Sidoni, Guido Bellezza, Lucio Crinò, Rita Chiari
Anaplastic lymphoma kinase (ALK) rearrangements represent the molecular driver of a subset of non-small cell lung cancers (NSCLCs). Despite the initial response, virtually all ALK-positive patients develop an acquired resistance to the ALK inhibitor crizotinib, usually within 12 months. Several next-generation ALK inhibitors have been developed in order to overcome crizotinib limitation, providing an unprecedented survival for this subset of patients. The aim of this review to summarize the current knowledge on ALK tyrosine kinase inhibitors (TKIs) in the treatment of advanced ALK-positive NSCLC, focusing on the role of novel ALK inhibitors in this setting...
April 17, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29666815/endobronchial-ultrasound-transbronchial-needle-aspiration-ebus-tbna-a-diagnostic-challenge-for-mediastinal-lesions
#2
REVIEW
Duilio Divisi, Gino Zaccagna, Mirko Barone, Francesca Gabriele, Roberto Crisci
Lung cancer is one of the most frequent neoplastic diseases. To date, most lung cancer is diagnosed at an advanced stage, making it difficult to choose the diagnostic and therapeutic strategy. Surgical resection represents the best therapeutic solution. However, the best results are obtained only in the early stages of the disease. Lymph node involvement conditions the treatment (surgical or non-surgical approach). Mediastinoscopy is an effective and widely used method for mediastinal staging but does not allow us to reach many mediastinal lymph nodes...
March 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29666811/immune-checkpoint-pathways-in-non-small-cell-lung-cancer
#3
REVIEW
Young Kwang Chae, Ayush Arya, Wade Iams, Marcello Cruz, Nisha Mohindra, Victoria Villaflor, Francis J Giles
Immunotherapy has evolved at a phenomenal pace in cancer therapeutics. This has primarily been fueled by the much perceived necessity to procure an alternative to current standard of care chemotherapy agents, owing to several concerns such as treatment-related toxicity and poor long-term survival associated with the same. The knowledge of various mechanisms involved in regulation of immune response to cancer cells has served a fundamental role in identifying key molecules through which immune cell activity may be modulated...
March 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29666453/epidemiology-and-survival-outcomes-of-mucinous-adenocarcinomas-a-seer-population-based-study
#4
Guang-Dong Xie, Yi-Rong Liu, Yi-Zhou Jiang, Zhi-Ming Shao
To investigate the epidemiology, demographics and survival of mucinous adenocarcinomas (MACs), we identified 80,758 MAC patients in the Surveillance, Epidemiology and End Results (SEER) database. The reported incidence of MACs ebbed and flowed over time; however, a significant increase in reported annual age-adjusted incidences of MACs in the appendix, lung and bronchus was observed from 1981 to 2014. The demographics and outcomes of MACs differed by anatomic sites. MACs of the stomach had the largest percentage of poorly differentiated or undifferentiated tumors (41...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29666298/delayed-autoimmune-toxicity-occurring-several-months-after-cessation-of-anti-pd-1-therapy
#5
Sagun Parakh, Jonathan Cebon, Oliver Klein
Treatment with anti-programmed cell death protein 1 (PD-1) antibodies has demonstrated clinical efficacy in a whole range of malignancies including advanced melanoma, renal cell cancer, bladder cancer, and non-small cell lung cancer. Immune-related adverse events are a unique side effect of checkpoint regulator therapy including anti-PD-1 antibodies. Treatment-related autoimmunity can occur in any organ system, with the median onset usually within 5-15 weeks from the commencement of therapy, depending on the organ system involved...
April 17, 2018: Oncologist
https://www.readbyqxmd.com/read/29666060/combo-therapy-for-lung-cancer-extends-survival
#6
(no author information available yet)
The PD-1 inhibitor pembrolizumab in combination with chemotherapy may be an effective therapy for patients with newly diagnosed advanced non-squamous non-small cell lung cancer. In a clinical trial, patients who received the combination had an estimated 12-month overall survival rate of 69.2%, compared with 49.4% in patients who received chemotherapy alone.
April 17, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29664358/tailored-management-of-stage-iiia-non-small-cell-lung-cancer-in-the-era-of-the-8th-edition-of-the-tnm-classification-for-lung-cancer
#7
Michael R Mueller
Stage IIIA is a very heterogeneous group encompassing locally advanced disease with T3 and T4 tumors without any nodal involvement and very small T1a primary tumors with unilateral mediastinal lymphatic disease. Tailored management defines interdisciplinary management requiring board decisions, which can sometimes be difficult particularly in stage IIIa non-small-cell lung cancer (NSCLC). Lobectomy still is standard of care even for stage I NSCLC, which increasingly is implemented using minimally invasive surgical technique...
March 2018: Future Oncology
https://www.readbyqxmd.com/read/29664357/surgery-for-advanced-lung-and-esophageal-cancer-new-horizons-or-false-dawn
#8
Marcello Migliore, Semih Halezeroglu, Antoon Lerut
No abstract text is available yet for this article.
March 2018: Future Oncology
https://www.readbyqxmd.com/read/29664192/cerebrospinal-fluid-markers-of-extracellular-matrix-remodeling-synaptic-plasticity-and-neuroinflammation-before-and-after-cranial-radiotherapy
#9
E Fernström, K Minta, U Andreasson, Å Sandelius, P Wasling, A Brinkmalm, K Höglund, K Blennow, J Nyman, H Zetterberg, M Kalm
BACKGROUND: Advances in the treatment of brain tumors have increased the number of long-term survivors, but at the cost of side effects following cranial radiotherapy ranging from neurocognitive deficits to outright tissue necrosis. At present, there are no tools reflecting the molecular mechanisms underlying such side effects, and thus no means to evaluate interventional effects after cranial radiotherapy. Therefore, fluid biomarkers is of great clinical interest. OBJECTIVE: Cerebrospinal fluid (CSF) levels of proteins involved in inflammatory signaling, synaptic plasticity and extracellular matrix (ECM) integrity were investigated following radiotherapy to the brain...
April 17, 2018: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29663291/apatinib-a-review-in-advanced-gastric-cancer-and-other-advanced-cancers
#10
Lesley J Scott
Apatinib [AiTan™ (China); Rivoceranib® (global)] is a novel, small molecule, selective vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor and is the second anti-angiogenic drug to be approved in China for the treatment of advanced or metastatic gastric cancer. This article summarizes the pharmacological properties of apatinib and reviews its clinical use in chemotherapy-experienced patients with advanced gastric adenocarcinoma, including gastroesophageal adenocarcinoma (GEA), or with other advanced cancers such as non-small cell lung cancer (NSCLC), breast cancer, gynaecological cancers, hepatocellular carcinoma (HCC), thyroid cancer and sarcomas...
April 16, 2018: Drugs
https://www.readbyqxmd.com/read/29662665/molecular-mechanism-of-action-and-potential-biomarkers-of-growth-inhibition-of-synergistic-combination-of-afatinib-and-dasatinib-against-gefitinib-resistant-non-small-cell-lung-cancer-cells
#11
Miao Wang, Alex Yuang-Chi Chang
Epidermal growth factor receptor - tyrosine kinase inhibitor (EGFR-TKI) is the first choice of treatment for advanced non-small cell lung cancer (NSCLC) patients harbouring activating EGFR mutations. However, single agent usually has limited efficacy due to heterogeneous resistant mechanisms of cancer cells. Thus drug combination therapy would offer more benefits by synergistic interactions and avoidance of resistance emergence. In this study, we selected 8 NSCLC cell lines with different genetic characteristics as research models to investigate the efficacy of 4 agents (gefitinib, cetuximab, afatinib and dasatinib) and their combinations...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29662663/impact-of-antibiotic-treatment-on-immune-checkpoint-blockade-efficacy-in-advanced-non-squamous-non-small-cell-lung-cancer
#12
Florian Huemer, Gabriel Rinnerthaler, Theresa Westphal, Hubert Hackl, Georg Hutarew, Simon Peter Gampenrieder, Lukas Weiss, Richard Greil
Introduction: Despite durable responses from immune-checkpoint blockade (ICB) in a subset of patients with advanced non-small cell lung cancer (NSCLC), the majority of patients do not derive benefit from this treatment. In this analysis we evaluated the impact of concomitant administration of antibiotics during initiation of ICB on clinical outcome. Methods: Advanced non-squamous NSCLC patients receiving ICB as second- or later line between 2015 and 2017 at our tertiary cancer center in Salzburg (Austria) were included...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29662657/5-nucleotidase-cn-ii-emerges-as-a-new-predictive-biomarker-of-response-to-gemcitabine-platinum-combination-chemotherapy-in-non-small-cell-lung-cancer
#13
Francesca Toffalorio, Mariacarmela Santarpia, Davide Radice, Christopher Adrian Jaramillo, Gianluca Spitaleri, Michela Manzotti, Chiara Catania, Lars Petter Jordheim, Giuseppe Pelosi, Godefridus J Peters, Carmelo Tibaldi, Niccola Funel, Lorenzo Spaggiari, Filippo de Braud, Tommaso De Pas, Elisa Giovannetti
A number of pharmacogenetic studies have been carried out in non-small-cell lung cancer (NSCLC) to identify and characterize genes involved in chemotherapy activity. However, the results obtained so far are controversial and no reliable biomarker is currently used to predict clinical benefit from platinum-based chemotherapy, which represents the cornerstone of treatment of advanced NSCLC. This study investigated the expression levels of ERCC1 and of six genes (RRM1, RRM2, hENT1, dCK, cN-II and CDA) involved in gemcitabine metabolism in locally/advanced NSCLC patients treated with gemcitabine/platinum combination...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29662612/exploiting-mitochondrial-and-metabolic-homeostasis-as-a-vulnerability-in-nf1-deficient-cells
#14
Robert J Allaway, Matthew D Wood, Sondra L Downey, Stephanie J Bouley, Nicole A Traphagen, Jason D Wells, Jaya Batra, Sir Norman Melancon, Carol Ringelberg, William Seibel, Nancy Ratner, Yolanda Sanchez
Neurofibromatosis type 1 is a disease caused by mutation of neurofibromin 1 ( NF1 ), loss of which results in hyperactive Ras signaling and a concomitant increase in cell proliferation and survival. Patients with neurofibromatosis type 1 frequently develop tumors such as plexiform neurofibromas and malignant peripheral nerve sheath tumors. Mutation of NF1 or loss of the NF1 protein is also observed in glioblastoma, lung adenocarcinoma, and ovarian cancer among other sporadic cancers. A therapy that selectively targets NF1 deficient tumors would substantially advance our ability to treat these malignancies...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29662549/tumour-necrosis-factor-interferon-gamma-and-interleukins-as-predictive-markers-of-antiprogrammed-cell-death-protein-1-treatment-in-advanced-non-small-cell-lung-cancer-a-pragmatic-approach-in-clinical-practice
#15
Efimia Boutsikou, Kalliopi Domvri, Georgia Hardavella, Dora Tsiouda, Konstantinos Zarogoulidis, Theodoros Kontakiotis
Background: The emergence of novel antiprogrammed cell death protein-1 (PD-1) inhibitors in non-small cell lung cancers (NSCLC) has revolutionized the therapeutic landscape of this disease. Although overall survival (OS) has improved in the first- and second-line therapy settings for advanced NSCLC, the benefit is not universal. In a climate of global scrutiny for healthcare costs and potential for toxicities related to immunotherapy, appropriate patient selection is crucial. The aim of this study was to evaluate potential prognostic and predictive biomarkers interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and a panel of interleukins (ILs) in the peripheral blood, and assess any correlation with response to anti-PD-1 inhibition, progression-free survival and OS in NSCLC patients...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29662547/pd-l1-expression-testing-in-non-small-cell-lung-cancer
#16
REVIEW
Cristina Teixidó, Noelia Vilariño, Roxana Reyes, Noemí Reguart
In recent years, immunotherapy has revolutionized and changed the standard of care in patients with advanced non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors, fundamentally those that act by blocking the programmed cell death receptor-1 (PD-1) and its ligand the programmed cell death ligand-1 (PD-L1) have emerged as novel treatment strategies in NSCLC, demonstrating undoubted superiority over chemotherapy in terms of efficacy. Several of these immune checkpoint modulators have recently gained regulatory approval for the treatment of advanced NSCLC, such as nivolumab, atezolizumab and pembrolizumab in first-line (only the latter) and second-line settings, and more recently, durvalumab as maintenance after chemoradiotherapy in locally advanced disease...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29662327/spotlight-on-dabrafenib-trametinib-in-the-treatment-of-non-small-cell-lung-cancer-place-in-therapy
#17
REVIEW
Thomas C Weart, Kenneth D Miller, Charles B Simone
Advanced non-small-cell lung cancer (NSCLC) remains a challenging disease. The limited utility of chemotherapy indicates the need for additional therapeutic options. Targeted therapy continues to be an important tool in the treatment of NSCLC. Mutations within the RAS-RAF-MEK-MAPK pathway, specifically the BRAF V600E mutation, have become an important target for the subset of NSCLC patients with this mutation. This paper summarizes the clinical evidence that lead to the recent approval of the combination of dabrafenib and trametinib to treat patients with advanced NSCLC who harbor a BRAF V600E mutation...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29661733/analysis-of-eml4-alk-rearrangement-in-non-small-cell-lung-cancer-in-argentina
#18
María Verzura, Emilio Batagelj, Claudia Bagnes, Claudio Martin, Diego Enrico, Eduardo Richardet, Paola De la Iglesia
INTRODUCTION: Identification of EML4-ALK rearrangement by FISH test has become standard in advanced NSCLC patients. There is limited information about the prevalence and clinical characteristics of ALK translocation in Latin America. The aim of our study was to evaluate this lung cancer subtype features in Argentinian patients and the factibility of FISH test with different methods used for obtaining tissue samples. METHODS: Between August 2014 and February 2017, 183 non-squamous NSCLC patients were prospectively enrolled from five Argentinian institutions...
February 26, 2018: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29661145/therapeutic-cancer-vaccine-phase-i-clinical-tolerance-study-of-hu-rhegf-rp64k-mont-in-patients-with-newly-diagnosed-advanced-non-small-cell-lung-cancer
#19
Puyuan Xing, Hongyu Wang, Sheng Yang, Xiaohong Han, Yan Sun, Yuankai Shi
BACKGROUND: Hu-rhEGF-rP64k/Mont is a biotechnology product for the treatment of advanced non-small cell lung cancer (NSCLC). The vaccine induces a neutralizing antibody-mediated immune response, against the normal circulating self-protein antigen epidermal growth factor (EGF), which prevents its binding to and activation of the EGF receptor, inhibiting the transduction of the signals that drive cancer cell proliferation, survival and spread. This phase I study aimed to evaluate the safety and the immunological response of Hu-rhEGF-rP64k vaccine in NSCLC patients...
April 16, 2018: BMC Immunology
https://www.readbyqxmd.com/read/29659668/cytology-cell-blocks-are-suitable-for-immunohistochemical-testing-for-pd-l1-in-lung-cancer
#20
H Wang, J Agulnik, G Kasymjanova, A Wang, V Cohen, D Small, C Pepe, L Sakr, P Fiset, M Auger, S Camilleri-Broet, M Alam El Din, G Chong, L van Kempen, A Spatz
Background: PD-L1 immunohistochemistry (IHC) testing is usually performed on tissue blocks from core needle biopsy or surgical resections. In this study, we assessed the feasibility of using cytology cell blocks for PD-L1 IHC assay. Methods: A total of 1419 consecutive cases of non-small cell lung cancer (NSCLC), including 371 cytology cell blocks, 809 small biopsies, and 239 surgical specimens, were included in the study. The cytology cell blocks were prepared with formalin only, methanol/alcohol only or both...
April 12, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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