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Immunotherapy lung cancer

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https://www.readbyqxmd.com/read/29917141/tumor-cdkn2a-associated-jak2-loss-and-susceptibility-to-immunotherapy-resistance
#1
Susanne Horn, Sonia Leonardelli, Antje Sucker, Dirk Schadendorf, Klaus G Griewank, Annette Paschen
Poor clinical responses to checkpoint blockade with anti-CTLA-4 and anti-PD-1 antibodies in melanoma have recently been associated with acquired IFNγ resistance that protects tumor cells from the antiproliferative and pro-apoptotic cytokine activity. IFNγ-resistant melanoma cells very often lack functional expression of the IFNγ signaling pathway gene JAK2 due to gene deletions or inactivating gene mutations. Analyzing melanoma cell lines (n = 46, applying next-generation targeted sequencing and single nucleotide polymorphism arrays) as well as available genomic data sets from The Cancer Genome Atlas (TCGA) tumor tissue samples (cutaneous melanoma n = 367, lung squamous cell carcinoma n = 501, bladder urothelial carcinoma n = 408, breast invasive carcinoma n = 768, colorectal adenocarcinoma n = 257), we demonstrate that the frequent chromosomal losses of the tumor suppressor CDKN2A in melanoma and other tumor entities enhance the susceptibility to IFNγ resistance by concomitant deletion of the JAK2 gene (odds ratio = 223...
June 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29915896/targeting-egfr-in-lung-cancer-current-standards-and-developments
#2
REVIEW
Asunción Díaz-Serrano, Pablo Gella, Elisabeth Jiménez, Jon Zugazagoitia, Luis Paz-Ares Rodríguez
Lung cancer is the second most common malignant tumor and the leading cause of cancer death. Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is a distinct subtype of lung cancer comprising approximately 15-40% of non-squamous tumors. The development of first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) has been a significant step forward in the treatment of patients with EGFR-mutant tumors, and over the last few years has been the therapy of choice in the initial management of patients with activating mutations in EGFR, with some differences in efficacy and toxicity profile...
June 18, 2018: Drugs
https://www.readbyqxmd.com/read/29915891/clinical-outcomes-of-african-american-patients-with-advanced-or-metastatic-non-small-cell-lung-cancer-on-nivolumab-in-a-single-community-based-cancer-center
#3
Andrew C Tiu, Rashmika Potdar, Djeneba Audrey Djibo, Muhammad Masab, Claudia Dourado
African Americans (AA) have the highest incidence and mortality rates with lung cancer. They are diagnosed at an earlier age with more advanced disease. Programmed cell death protein-1 inhibitor, Nivolumab, was approved as a second-line agent after failure of platinum-based therapy for advanced or metastatic non-small cell lung cancer (NSCLC). The original studies leading to the approval of Nivolumab had insufficient AA patients, thus there is still inadequate knowledge on treatment outcomes among AA patients...
June 18, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29911108/emerging-application-of-genomics-guided-therapeutics-in-personalized-lung-cancer-treatment
#4
REVIEW
Aubhishek Zaman, Trever G Bivona
In lung cancer, genomics-driven comprehensive molecular profiling has identified novel chemically and immunologically addressable vulnerabilities, resulting in an increasing application of precision medicine by targeted inactivation of tumor oncogenes and immunogenic activation of host anti-tumor surveillance as modes of treatment. However, initially profound response of these targeted therapies is followed by relapse due to therapy-resistant residual disease states. Although distinct mechanisms and frameworks for therapy resistance have been proposed, accounting for and upfront prediction of resistance trajectories has been challenging...
May 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29910653/brain-metastases-in-non-small-cell-lung-cancer-are-tyrosine-kinase-inhibitors-and-checkpoint-inhibitors-now-viable-options
#5
REVIEW
S Morin-Ben Abdallah, A Wong
Significant progress has been made in the treatment of stage iv non-small-cell lung cancer (nsclc); however, the prognosis of patients with brain metastases remains poor. Resection and radiation therapy remain standard options. This issue is an important one because 10% of patients with nsclc have brain metastases at diagnosis, and 25%-40% develop brain metastases during their disease. Standard chemotherapy does not cross the blood-brain barrier. However, there is new hope that tyrosine kinase inhibitors (tkis) used in patients with identified targetable mutations such as mutations of EGFR and rearrangements of ALK could have activity in the central nervous system (cns)...
June 2018: Current Oncology
https://www.readbyqxmd.com/read/29910652/current-landscape-of-immunotherapy-for-the-treatment-of-metastatic-non-small-cell-lung-cancer
#6
REVIEW
A Pabani, C A Butts
For patients with advanced non-small-cell lung cancer (nsclc) lacking a targetable molecular driver, the mainstay of treatment has been cytotoxic chemotherapy. The survival benefit of chemotherapy in this setting is modest and comes with the potential for significant toxicity. The introduction of immunotherapeutic agents targeting the programmed cell death 1 protein (PD-1) and the programmed cell death ligand 1 (PD-L1) has drastically changed the treatment paradigms for these patients. Three agents-atezolizumab, nivolumab, and pembrolizumab-have been shown to be superior to chemotherapy in the second-line setting...
June 2018: Current Oncology
https://www.readbyqxmd.com/read/29910650/algorithm-for-the-treatment-of-advanced-or-metastatic-squamous-non-small-cell-lung-cancer-an-evidence-based-overview
#7
REVIEW
N Daaboul, G Nicholas, S A Laurie
The treatment of squamous non-small-cell lung cancer (nsclc) is evolving. In the past, the backbone of treatment was chemotherapy, with very few other options available. Fortunately, that situation is changing, especially with a better understanding of tumour biology. Various strategies have been tried to improve patient outcomes. The most notable advance must be immunotherapy, which has revolutionized the treatment paradigm for lung cancer in patients without a driver mutation. Immunotherapy is now the treatment of choice in patients who have progressed after chemotherapy and is replacing chemotherapy as upfront therapy in a selected population...
June 2018: Current Oncology
https://www.readbyqxmd.com/read/29910649/rapidly-changing-treatment-algorithms-for-metastatic-nonsquamous-non-small-cell-lung-cancer
#8
REVIEW
B Melosky
Background: The treatment paradigm for metastatic nonsquamous non-small-cell lung cancer (nsclc) continues to change. Algorithms published only 6 months ago are outdated today and are dramatically different from those published a few years ago. New driver mutations continue to be identified, and the development of therapies to inhibit oncogenic addiction is ongoing. Patient survival is improving as treatments become more personalized and effective. Methods: This review looks at the outcomes of recent trials and discusses treatment options for patients with metastatic nsclc of nonsquamous histology...
June 2018: Current Oncology
https://www.readbyqxmd.com/read/29909021/nf%C3%AE%C2%BAb-in-pancreatic-stellate-cells-reduces-infiltration-of-tumors-by-cytotoxic-t-cells-and-killing-of-cancer-cells-via-upregulation-of-cxcl12
#9
Bharti Garg, Bhuwan Giri, Shrey Modi, Vrishketan Sethi, Iris Castro, Oliver Umland, Yuguang Ban, Shweta Lavania, Rajinder Dawra, Sulagna Banerjee, Selwyn Vickers, Nipun B Merchant, Steven Xi Chen, Eli Gilboa, Sundaram Ramakrishnan, Ashok Saluja, Vikas Dudeja
BACKGROUND & AIMS: Immunotherapies are ineffective against pancreatic cancer. We investigated whether the activity of nuclear factor (NF)κB in pancreatic stromal cells contributes to an environment that suppresses anti-tumor immune response. METHODS: Pancreata of C57BL/6 or Rag1-/- mice were given pancreatic injections of a combination of KrasG12D/+; Trp53 R172H/+; Pdx-1cre (KPC) pancreatic cancer cells and pancreatic stellate cells (PSCs) extracted from C57BL/6 (control) or mice with disruption of the gene encoding the NFkB p50 subunit (Nfkb1 or p50-/- mice)...
June 14, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29908541/construction-of-a-recombinant-phage-vaccine-capable-of-reducing-the-growth-rate-of-an-established-ll2-tumor-model
#10
Majid Asadi-Ghalehni, Mohamad Javad Rasaee, Nabiollah Namvar Asl, Masood Khosravani, Masoumeh Rajabibazl, Saeed Khalili, Helmout Modjtahedi, Esmaeil Sadroddiny
Over expression of the epidermal growth factor receptor (EGFR) in many human epithelial tumors has been correlated with disease progression and poor prognosis. EGFR-inhibiting immunotherapy has already been introduced in cancer therapy. Peptide displaying phage particles in eukaryotic hosts can behave as antigen carriers, able to activate the innate immune system and to elicit adaptive immunity. Herein, the M13-pAK8-VIII phagemid plasmid was engineered to contain the sequences for an EGFR mimotope along with the L2 extracellular domain of EGFR (EM-L2) which would produce the final peptide-phage vaccine...
June 2018: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29907821/new-windows-open-for-immunotherapy-in-lung-cancer
#11
Lizza Hendriks, Benjamin Besse
No abstract text is available yet for this article.
June 2018: Nature
https://www.readbyqxmd.com/read/29905778/predictive-biomarkers-for-response-to-egfr-directed-monoclonal-antibodies-for-advanced-squamous-cell-lung-cancer
#12
P D Bonomi, D Gandara, F R Hirsch, K M Kerr, C Obasaju, L Paz-Ares, C Bellomo, J D Bradley, P A Bunn, M Culligan, J R Jett, E S Kim, C J Langer, R B Natale, S Novello, M Pérol, S S Ramalingam, M Reck, C H Reynolds, E F Smit, M A Socinski, D R Spigel, J F Vansteenkiste, H Wakelee, N Thatcher
Background: Upregulated expression and aberrant activation of the epidermal growth-factor receptor (EGFR) are found in lung cancer, making EGFR a relevant target for non-small-cell lung cancer (NSCLC). Treatment with anti-EGFR monoclonal antibodies (mAbs) is associated with modest improvement in overall survival in patients with squamous cell lung cancer (SqCLC) who have a significant unmet need for effective treatment options. While there is evidence that using EGFR gene copy number, EGFR mutation, and EGFR protein expression as biomarkers can help select patients who respond to treatment, it is important to consider biomarkers for response in patients treated with combination therapies that include EGFR mAbs...
June 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29904031/immunotherapy-in-non-small-cell-lung-cancer-shifting-prognostic-paradigms
#13
REVIEW
Megan B Barnet, Wendy A Cooper, Michael J Boyer, Steven Kao
Immune checkpoint inhibitors have shown efficacy in the treatment of non-small cell lung cancer (NSCLC) in the adjuvant, first- and subsequent-line settings. In metastatic disease, they provide hope of durable response where “best-case” scenario has long been inadequate. This progress has highlighted the immunogenic nature of NSCLC and invigorated research into immunotherapy in the field. In this review we consider the foundations of immunotherapy in NSCLC, canvass the current research and summarise the evidence guiding clinical practice...
June 14, 2018: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/29901069/prognostic-value-of-magea4-in-primary-lung-cancer-depends-on-subcellular-localization-and-p53-status
#14
Aki Fujiwara-Kuroda, Tatsuya Kato, Takehiro Abiko, Takahiro Tsuchikawa, Noriaki Kyogoku, Masaomi Ichinokawa, Kimitaka Tanaka, Takehiro Noji, Yasuhiro Hida, Kichizo Kaga, Yoshiro Matsui, Hiroaki Ikeda, Shinichi Kageyama, Hiroshi Shiku, Satoshi Hirano
Melanoma antigen family A4 (MAGEA4), a cancer/testis antigen, is overexpressed and is thus an immunotherapy target in various malignant tumors, including non-small cell lung cancer. However, whether MAGEA4 induces or inhibits the apoptosis of lung cancer cells remains controversial, as is its prognostic significance, particularly since there is no reliable method with which to detect MAGEA4 specifically. In this study, we optimized assay conditions to detect MAGEA4 based on cells transiently transfected with MAGEA genes, and found that MAGEA4 was expressed in four of eight non-small cell lung cancer cell lines, and in 25...
May 31, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29900054/large-scale-database-mining-reveals-hidden-trends-and-future-directions-for-cancer-immunotherapy
#15
Jakob Nikolas Kather, Anna Sophie Berghoff, Dyke Ferber, Meggy Suarez-Carmona, Constantino Carlos Reyes-Aldasoro, Nektarios A Valous, Rodrigo Rojas-Moraleda, Dirk Jäger, Niels Halama
Cancer immunotherapy has fundamentally changed the landscape of oncology in recent years and significant resources are invested into immunotherapy research. It is in the interests of researchers and clinicians to identify promising and less promising trends in this field in order to rationally allocate resources. This requires a quantitative large-scale analysis of cancer immunotherapy related databases. We developed a novel tool for text mining, statistical analysis and data visualization of scientific literature data...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29900040/differential-regulation-of-t-cell-mediated-anti-tumor-memory-and-cross-protection-against-the-same-tumor-in-lungs-versus-skin
#16
Jessica J O'Konek, Elena Ambrosino, Anja C Bloom, Lise Pasquet, Chandirasegaran Massilamany, Zheng Xia, Masaki Terabe, Jay A Berzofsky
A major advantage of immunotherapy of cancer is that effector cells induced at one site should be able to kill metastatic cancer cells in other sites or tissues. However, different tissues have unique immune components, and very little is known about whether effector T cells induced against tumors in one tissue can work against the same tumors in other tissues. Here, we used CT26 murine tumor models to investigate anti-tumor immune responses in the skin and lungs and characterized cross-protection between the two tissues...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29899191/tumor-mutational-burden-analysis-of-2-000-japanese-cancer-genomes-using-whole-exome-and-targeted-gene-panel-sequencing
#17
Keiichi Hatakeyama, Takeshi Nagashima, Kenichi Urakami, Keiichi Ohshima, Masakuni Serizawa, Sumiko Ohnami, Yuji Shimoda, Shumpei Ohnami, Koji Maruyama, Akane Naruoka, Yasuto Akiyama, Masatoshi Kusuhara, Tohru Mochizuki, Ken Yamaguchi
Tumor mutational burden (TMB) is an emerging characteristic in cancer and has been associated with microsatellite instability, defective DNA replication/repair, and response to PD-1 and PD-L1 blockade immunotherapy. When estimating TMB, targeted panel sequencing is performed using a few hundred genes; however, a comparison of TMB results obtained with this platform and with whole exome sequencing (WES) has not been performed for various cancer types. In the present study, we compared TMB results using the above two platforms in 2,908 solid tumors that were obtained from Japanese patients...
2018: Biomedical Research
https://www.readbyqxmd.com/read/29896282/aerosol-immunotherapy-with-or-without-cisplatin-for-metastatic-lung-cancer-non-small-cell-lung-cancer-disease-in-vivo-study-a-more-efficient-combination
#18
Konstantinos Sapalidis, Paul Zarogoulidis, Efstathios Pavlidis, Stella Laskou, Athanasios Katsaounis, Charilaos Koulouris, Dimitrios Giannakidis, Stylianos Mantalovas, Haidong Huang, Chong Bai, Yuting Wen, Li Wang, Chrysanthi Sardeli, Aikaterini Amaniti, Ilias Karapantzos, Chrysanthi Karapantzou, Wolfgang Hohenforst-Schmidt, Fotis Konstantinou, Isaak Kesisoglou, Naim Benhanseen
Lung cancer is the leading cause of cancer death after prostate cancer for males and breast cancer for females. There are novel therapies in the past five years such as; tyrosine kinase inhibitors and most recently in the last two years immunotherapy. Immunotherapy is currently being investigated if it can be administered alone or in combination. Previously we have investigated whether immunotherapy compounds can be produced as aerosols, and in the current study we investigated the safety and efficiency independently of the programmed death-ligand 1...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29892522/blockade-of-ccl2-enhances-immunotherapeutic-effect-of-anti-pd1-in-lung-cancer
#19
Yue Wang, Xiaokai Zhang, Liangliang Yang, Jinru Xue, Guangrui Hu
Myeloid derived suppressor cells (MDSC) play a pivotal role in tumor immune evasion and MDSC levels increased in patients with cancer. Studies confirmed the associations between MDSC and various cytokines in the peripheral blood. However, little is known about the association between parenchymal MDSC subsets and cytokines, or the mechanism drawing MDSC into tumor parenchyma. This study was to analyze the correlation between MDSC subsets and CCL2 level in lung cancer model. G-MDSC and M-MDSC from the blood and parenchyma were analyzed by flow cytometry and western blot in the lung tumor model...
June 2018: Journal of Bone Oncology
https://www.readbyqxmd.com/read/29892061/mutations-in-the-swi-snf-complex-induce-a-targetable-dependence-on-oxidative-phosphorylation-in-lung-cancer
#20
Yonathan Lissanu Deribe, Yuting Sun, Christopher Terranova, Fatima Khan, Juan Martinez-Ledesma, Jason Gay, Guang Gao, Robert A Mullinax, Tin Khor, Ningping Feng, Yu-Hsi Lin, Chia-Chin Wu, Claudia Reyes, Qian Peng, Frederick Robinson, Akira Inoue, Veena Kochat, Chang-Gong Liu, John M Asara, Cesar Moran, Florian Muller, Jing Wang, Bingliang Fang, Vali Papadimitrakopoulou, Ignacio I Wistuba, Kunal Rai, Joseph Marszalek, P Andrew Futreal
Lung cancer is a devastating disease that remains a top cause of cancer mortality. Despite improvements with targeted and immunotherapies, the majority of patients with lung cancer lack effective therapies, underscoring the need for additional treatment approaches. Genomic studies have identified frequent alterations in components of the SWI/SNF chromatin remodeling complex including SMARCA4 and ARID1A. To understand the mechanisms of tumorigenesis driven by mutations in this complex, we developed a genetically engineered mouse model of lung adenocarcinoma by ablating Smarca4 in the lung epithelium...
June 8, 2018: Nature Medicine
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