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https://www.readbyqxmd.com/read/28725482/systems-biology-driving-drug-development-from-design-to-the-clinical-testing-of-the-anti-erbb3-antibody-seribantumab-mm-121
#1
REVIEW
Birgit Schoeberl, Art Kudla, Kristina Masson, Ashish Kalra, Michael Curley, Gregory Finn, Emily Pace, Brian Harms, Jaeyeon Kim, Jeff Kearns, Aaron Fulgham, Olga Burenkova, Viara Grantcharova, Defne Yarar, Violette Paragas, Jonathan Fitzgerald, Marisa Wainszelbaum, Kip West, Sara Mathews, Rachel Nering, Bambang Adiwijaya, Gabriela Garcia, Bill Kubasek, Victor Moyo, Akos Czibere, Ulrik B Nielsen, Gavin MacBeath
The ErbB family of receptor tyrosine kinases comprises four members: epidermal growth factor receptor (EGFR/ErbB1), human EGFR 2 (HER2/ErbB2), ErbB3/HER3, and ErbB4/HER4. The first two members of this family, EGFR and HER2, have been implicated in tumorigenesis and cancer progression for several decades, and numerous drugs have now been approved that target these two proteins. Less attention, however, has been paid to the role of this family in mediating cancer cell survival and drug tolerance. To better understand the complex signal transduction network triggered by the ErbB receptor family, we built a computational model that quantitatively captures the dynamics of ErbB signaling...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28717395/brain-imaging-before-primary-lung-cancer-resection-a-controversial-topic
#2
Zoe Hudson, Eveline Internullo, Anthony Edey, Isabel Laurence, Davide Bianchi, Alfredo Addeo
OBJECTIVE: International and national recommendations for brain imaging in patients planned to undergo potentially curative resection of non-small-cell lung cancer (NSCLC) are variably implemented throughout the United Kingdom [Hudson BJ, Crawford MB, and Curtin J et al (2015) Brain imaging in lung cancer patients without symptoms of brain metastases: a national survey of current practice in EnglandClin Radiol https://doi.org/10.1016/j.crad.2015.02.007]. However, the recommendations are not based on high-quality evidence and do not take into account cost implications and local resources...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28712427/depression-inflammation-and-epidermal-growth-factor-receptor-egfr-status-in-metastatic-non-small-cell-lung-cancer-a-pilot-study
#3
Jamie M Jacobs, Lara Traeger, Justin Eusebio, Naomi M Simon, Lecia V Sequist, Joseph A Greer, Jennifer S Temel, William F Pirl
OBJECTIVE: Patients with stage IV non-small cell lung cancer (NSCLC) have high risk for depressive symptoms and major depressive disorder (MDD); however, those with epidermal growth factor receptor (EGFR) mutations may have decreased risk. The biological underpinning of this relationship is unknown. We examined differences in depression severity and MDD in patients with newly diagnosed stage IV NSCLC based on EGFR mutation status, and examined proinflammatory cytokines and growth factors known to play a role in cancer progression and depression...
August 2017: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/28709816/-current-knowledge-on-perioperative-treatments-of-non-small-cell-lung-carcinomas
#4
REVIEW
S Brosseau, C Naltet, M Nguenang, V Gounant, P Mordant, B Milleron, Y Castier, G Zalcman
Surgery is still the main treatment in early-stage of non-small cell lung cancer with 5-year survival of stage IA patients exceeding 80%, but 5-year survival of stage II patients rapidly decreasing with tumor size, N status, and visceral pleura invasion. The major metastatic risk in such patients has supported clinical research assessing systemic or loco-regional perioperative treatments. Modern phase 3 trials clearly validated adjuvant or neo-adjuvant platinum-based chemotherapy in resected stage I-III patients as a standard treatment of which value has been reassessed several independent meta-analyses, showing a 5% benefit in 5y-survival, and a decrease of the relative risk for death around from 12 to 25%...
July 11, 2017: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/28709663/pulmonary-resection-for-second-lung-cancer-after-pneumonectomy-a-population-based-study
#5
Adil Ayub, Sadiq S Rehmani, Adnan M Al-Ayoubi, Wissam Raad, Raja M Flores, Faiz Y Bhora
BACKGROUND: Pulmonary resection for a second lung cancer after pneumonectomy is generally considered to be at prohibitive risk. Using a population-based database, we examined treatment patterns and survival in patients who underwent pulmonary resection after pneumonectomy for lung cancer. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER) database (1988-2012) to identify patients who underwent pneumonectomy and subsequently experienced contralateral non-small cell lung cancer (NSCLC)...
July 11, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28707167/supportive-care-for-patients-undergoing-immunotherapy
#6
Bernardo Leon Rapoport, Ronwyn van Eeden, Vincent Sibaud, Joel B Epstein, Jean Klastersky, Matti Aapro, Devan Moodley
Immune checkpoint inhibitors, a new class of cancer therapeutic agents, play an important role in the management of melanoma, NSCLC, and other malignancies. A workshop organized by three MASCC Study Groups: Oral Care, Skin Toxicities, and Neutropenia, Infection, and Myelosuppression during the MASCC Annual Meeting held in Adelaide, Australia on 23-25 June, 2016 focused on the new class of anti-cancer therapeutic agents. Topics in the workshop included the mechanism of action and clinical uses of immune anti-CTL4 and anti-PD1 antibodies, checkpoint inhibitor toxicities, including skin adverse events, gastrointestinal toxicities, oral complications, pulmonary toxicities, and endocrinological and immune-related infections...
July 13, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28707078/ctla-4-expression-in-the-non-small-cell-lung-cancer-patient-tumor-microenvironment-diverging-prognostic-impact-in-primary-tumors-and-lymph-node-metastases
#7
Erna-Elise Paulsen, Thomas K Kilvaer, Mehrdad Rakaee, Elin Richardsen, Sigurd M Hald, Sigve Andersen, Lill-Tove Busund, Roy M Bremnes, Tom Donnem
The immune checkpoint receptor CTLA-4 plays a crucial part in negatively regulating T cell activation and maintaining self-tolerance. It is frequently overexpressed in a variety of malignancies, yet its prognostic impact in non-small cell lung cancer (NSCLC) remains unclear. We constructed tissue microarrays from tumor tissue samples and evaluated the immunohistochemical expression of CTLA-4 in 536 patients with primary resected stage I-IIIA NSCLC. Expression of CTLA-4 was analyzed in tumor and stromal primary tumor tissue and in locoregional metastatic lymph nodes...
July 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28706163/clinical-outcomes-of-wbrt-plus-egfr-tkis-versus-wbrt-or-tkis-alone-for-the-treatment-of-cerebral-metastatic-nsclc-patients-a-meta-analysis
#8
Hong Zheng, Quan-Xing Liu, Bin Hou, Dong Zhou, Jing-Meng Li, Xiao Lu, Qiu-Ping Wu, Ji-Gang Dai
Whether WBRT plus EGFR-TKIs has a greater survival benefit than EGFR-TKIs alone or WBRT alone remains controversial in NSCLC patients with multiple brain metastases. To rectify this, we conducted a systematic meta-analysis based on 9 retrospective studies and 1 randomized controlled study published between 2012 and 2016, comprising 1041 patients. Five studies were included in the comparison of WBRT plus EGFR-TKIs and EGFR-TKIs alone. The combined HR for OS of patients with EGFR mutation was 1.25 [95% CI 0.98-2...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28699084/egfr-mutation-testing-of-non-squamous-nsclc-impact-and-uptake-during-implementation-of-testing-guidelines-in-a-population-based-registry-cohort-from-northern-new-zealand
#9
Mark McKeage, Mark Elwood, Sandar Tin Tin, Prashannata Khwaounjoo, Phyu Aye, Angie Li, Karen Sheath, Phillip Shepherd, George Laking, Nicola Kingston, Christopher Lewis, Donald Love
BACKGROUND: Since 2013, clinical practice guidelines recommend EGFR mutation testing of non-squamous NSCLC to select advanced-stage patients for first-line treatment using EGFR-TKIs. OBJECTIVE: We aimed to determine population-based trends in the real-world uptake and impact in routine practice of these recently updated testing guidelines. PATIENTS AND METHODS: A population-based observational study was conducted of notifications to the New Zealand Cancer Registry of patients eligible for EGFR testing diagnosed in northern New Zealand between January 2010 and April 2014...
July 11, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28698503/cd15s-cd62e-interaction-mediates-the-adhesion-of-non-small-cell-lung-cancer-cells-on-brain-endothelial-cells-implications-for-cerebral-metastasis
#10
Samah A Jassam, Zaynah Maherally, James R Smith, Keyoumars Ashkan, Federico Roncaroli, Helen L Fillmore, Geoffrey J Pilkington
Expression of the cell adhesion molecule (CAM), Sialyl Lewis X (CD15s) correlates with cancer metastasis, while expression of E-selectin (CD62E) is stimulated by TNF-α. CD15s/CD62E interaction plays a key role in the homing process of circulating leukocytes. We investigated the heterophilic interaction of CD15s and CD62E in brain metastasis-related cancer cell adhesion. CD15s and CD62E were characterised in human brain endothelium (hCMEC/D3), primary non-small cell lung cancer (NSCLC) (COR-L105 and A549) and metastatic NSCLC (SEBTA-001 and NCI-H1299) using immunocytochemistry, Western blotting, flow cytometry and immunohistochemistry in human brain tissue sections...
July 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28693444/the-value-of-ultrasound-guided-biopsy-of-fluorodeoxy-glucose-positron-emission-tomography-fdg-pet-positive-supraclavicular-lymph-nodes-in-patients-with-suspected-lung-cancer
#11
Lennart Werner, Franziska Aebersold Keller, Ujwal Bhure, Justus Egidius Roos, Katharina Tornquist, Maria Del Sol Pèrez-Lago, Oliver Gautschi, Klaus Strobel
BACKGROUND: Accurate lymph node staging is essential for adequate prognostication and therapy planning in patients with non-small cell lung cancer (NSCLC). FDG-PET/CT is a sensitive tool for the detection of metastases, including non-palpable supraclavicular lymph node (SCLN) metastases. Histological proof of metastatic spread and mutation analysis is crucial for optimal staging and therapy. The aim of this study was to investigate the value of ultrasound-guided fine needle aspiration cytology (FNAC) and core biopsy (CB) of FDG active, non-palpable SCLN's in patients with suspicion for lung cancer...
July 11, 2017: BMC Medical Imaging
https://www.readbyqxmd.com/read/28680960/efficacy-and-safety-results-of-the-afatinib-expanded-access-program
#12
Edward S Kim, Balazs Halmos, Ingrid F Kohut, Taral Patel, Regan D Rostorfer, Alexander I Spira, Agnieszka Cseh, John McKay, Gudrun Wallenstein, Kathryn F Mileham
INTRODUCTION: Afatinib is an oral, irreversible ErbB family blocker approved for first-line treatment of metastatic epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). The expanded access program (EAP) allowed early access to afatinib and provided additional data on its safety, tolerability, and efficacy. METHODS: The afatinib EAP was an open-label, multicenter, single-arm program in the United States that treated and followed patients with locally advanced or metastatic NSCLC harboring EGFR mutations...
2017: Oncology and Therapy
https://www.readbyqxmd.com/read/28680534/nsclc-depend-upon-yap-expression-and-nuclear-localization-after-acquiring-resistance-to-egfr-inhibitors
#13
Marc McGowan, Lilach Kleinberg, Ann Rita Halvorsen, Åslaug Helland, Odd Terje Brustugun
Yes-associated protein (YAP) is a downstream target of the Hippo pathway and has been found to be oncogenic driving many cancers into developing metastatic phenotypes leading to poor survival outcomes. This study investigated if YAP expression is associated with drug resistance in two non-small cell lung cancer (NSCLC) lines (HCC827 and H1975) generated to become resistant to the EGFR tyrosine kinase inhibitors (EGFR TKI) erlotinib, gefitinib or the T790M-specific osimertinib. We found that acquired EGFR TKI resistance was associated with YAP over-expression (osimertinib-resistant cells) or YAP amplification (erlotinib- and gefitinib-resistant cells) along with EMT phenotypic changes...
March 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28680205/an-unusual-case-of-myocardial-localization-of-non-small-cell-lung-cancer-metastasis-a-case-report-and-review-of-literature
#14
Luca Tagliabue, Giulia Manfrinato, Andrea Luciani
Positron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG) is useful for staging non-small cell lung cancer (NSCLC), decide the appropriate initial management, and evaluate the response to therapy. Metastatic spreading is very common during the course of NSCLC and principal localization sites include: regional and mediastinal lymph nodes and organs such as the contralateral lung parenchyma, bone, brain, adrenal gland, pleura, and liver. Myocardial localizations are very rare, often asymptomatic, and difficult to diagnose...
July 2017: Indian Journal of Nuclear Medicine: IJNM: the Official Journal of the Society of Nuclear Medicine, India
https://www.readbyqxmd.com/read/28676215/identification-of-a-novel-t1151k-alk-mutation-in-a-patient-with-alk-rearranged-nsclc-with-prior-exposure-to-crizotinib-and-ceritinib
#15
Viola W Zhu, J Jean Cui, Maria Fernandez-Rocha, Alexa B Schrock, Siraj M Ali, Sai-Hong Ignatius Ou
Patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) derive significant clinic benefit from treatment with ALK inhibitors. Crizotinib was the first approved tyrosine kinase inhibitor (TKI) for this distinct molecular subset of NSCLC. Disease progression on TKI inevitably arises secondary to diverse resistance mechanisms among which emergence of secondary ALK mutations is one of many ways in which tumor cells have adapted to survive. Therefore there is a clinical imperative to identify acquired ALK mutations via repeat tissue biopsy if clinically feasible...
August 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28673332/a-multicenter-survey-of-first-line-treatment-patterns-and-gene-aberration-test-status-of-patients-with-unresectable-stage-iiib-iv-nonsquamous-non-small-cell-lung-cancer-in-china-ctong-1506
#16
Qing Zhou, Yong Song, Xin Zhang, Gong-Yan Chen, Dian-Sheng Zhong, Zhuang Yu, Ping Yu, Yi-Ping Zhang, Jian-Hua Chen, Yi Hu, Guo-Sheng Feng, Xia Song, Qiang Shi, Lu Lu Yang, Ping Hai Zhang, Yi-Long Wu
BACKGROUND: In recent years, systemic chemotherapy and molecular targeted therapy have become standard first-line treatments for locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC). The objective of this survey was to investigate first-line anticancer treatment patterns and gene aberration test status of patients with advanced nonsquamous NSCLC in China. METHODS: Patients included in this study had unresectable Stage IIIB/IV nonsquamous NSCLC and were admitted during August 2015 to March 2016 into one of 12 tertiary hospitals throughout China for first-line anticancer treatment...
July 3, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28670367/silencing-of-advanced-glycosylation-and-glycosylation-and-product-specific-receptor-rage-inhibits-the-metastasis-and-growth-of-non-small-cell-lung-cancer
#17
Yan Xia Yu, Wen Chong Pan, Yu Feng Cheng
Non-small cell lung cancer (NSCLC) constitutes the main cases of lung cancer and is the world's most common and lethal cancer owing to regional invasion or distant metastasis. Growing morbidity and lethality demonstrates that valid molecular target in management of NSCLC metastasis is still absence. The receptor of advanced glycation end-products (RAGE) has been identified as an oncogenic gene and appears to promote the growth and metastasis of various cancers. Here, we investigated if RAGE targeted by RNA interference (RNAi) might have certain effect on the restraint of the growth of NSCLC and tumor metastasis...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28668822/when-cancer-patients-suddenly-have-a-positive-pregnancy-test
#18
Daniela Groza, Donat Duerr, Mathias Schmid, Beatrix Boesch
We present the case of non-small cell lung cancer (NSCLC) in a 48-year-old woman with an active history of smoking. The patient initially presented to her general practitioner with a progressive swelling on the neck. Further investigations diagnosed a metastatic lung tumour, and palliative chemotherapy was started. After 5 months of treatment, by newly reported amenorrhoea, cautiously before a restaging CT scan of the abdomen, a pregnancy test was performed and was positive. Both the gynaecological examination and the hormonal panel yielded no signs of pregnancy...
July 1, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28668205/an-evolving-algorithm-to-select-and-sequence-therapies-in-egfr-mutation-positive-nsclc-a-strategic-approach
#19
Barbara Melosky, Sanjay Popat, David R Gandara
The optimal treatment sequence for patients with metastatic epidermal growth factor receptor (EGFR) mutation-positive (EGFR-M(+)) non-small-cell lung cancer (NSCLC) continues to evolve, related largely to an increasing number of breakthroughs and studies in the field. The efficacy of tyrosine kinase inhibitors in the treatment of these patients is well established; however, the treatment decision-making process is becoming more complex as our knowledge of EGFR mutations and resistance pathways grows and more treatment options become available...
June 8, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28662869/radiation-and-pd-1-inhibition-favorable-outcomes-after-brain-directed-radiation
#20
Luke R G Pike, Andrew Bang, Patrick Ott, Tracy Balboni, Allison Taylor, Paul Catalano, Bhupendra Rawal, Alexander Spektor, Monica Krishnan, Daniel Cagney, Brian Alexander, Ayal A Aizer, Elizabeth Buchbinder, Mark Awad, Leena Gandhi, F Stephen Hodi, Jonathan D Schoenfeld
BACKGROUND AND PURPOSE: Patients with metastatic melanoma, renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC) are increasingly treated with immune checkpoint blockade targeting the programed death (PD)-1 receptor, often with palliative radiation therapy. Outcome data are limited in this population. MATERIAL AND METHODS: We retrospectively reviewed consecutive patients with metastatic NSCLC, melanoma, and RCC who received radiation and anti-PD-1 therapy at four centers...
June 26, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
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