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Targeted therapy lung cancer

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https://www.readbyqxmd.com/read/29792799/in-vivo-evaluation-of-reduction-responsive-alendronate-hyaluronan-curcumin-polymer-drug-conjugates-for-targeted-therapy-of-bone-metastatic-breast-cancer
#1
Kaili Wang, Chunjing Guo, Xue Dong, Yueming Yu, Bingjie Wang, Wanhui Liu, Daquan Chen
Many cancers such as human breast cancer and lung cancer easily metastasize to bones, leading to the formation of secondary tumors in advanced stage. Based on the CD44-targeted effect of oHA and bone-targeted effect of ALN, we prepared a reduction-responsive, CD44 receptor-targeting and bone-targeting nano-micelle, called CUR-loaded ALN-oHA-S-S-CUR micelles. In this study, we aimed to evaluate the antitumor activity and bone-targeting ability of CUR-loaded ALN-oHA-S-S-CUR micelles. The in vivo experiment results showed that a larger number of micelles was gathered in the bone metastatic tumor tissue and reduced the bone destruction...
May 24, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29790694/advances-in-antibody-therapeutics-targeting-small-cell-lung-cancer
#2
REVIEW
Hongyang Lu, Zhiming Jiang
The proportion of small-cell lung cancer (SCLC) among all lung cancers decreased from 17.26% in 1986 to 12.95% in 2002. Chemotherapy is the key mode of treatment. However, novel therapeutic strategies and drugs are imperative, as the prognosis remains poor. In recent years, antibody therapies have shown promising prospects against malignancy. This review focuses on the advances in antibody therapies in SCLC. Although the results of pembrolizumab, nivolumab, ipilimumab, and rovalpituzumab tesirine are inspiring, all of the clinical trials on these drugs are phase I/II and have been verified for further phase III clinical trials...
May 16, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29789556/foxm1-dependent-rad51-and-brca2-signaling-protects-idiopathic-pulmonary-fibrosis-fibroblasts-from-radiation-induced-cell-death
#3
Jintaek Im, Jessica Lawrence, Davis Seelig, Richard S Nho
Radiation therapy is critical for the control of many tumors and lung is an important dose-limiting organ that impacts radiation dose prescribed to avoid irreversible pulmonary fibrosis in cancer survivors. Idiopathic pulmonary fibrosis (IPF) is a chronic, irreversible lung disease caused by aberrantly activated lung (myo)fibroblasts. The presence of pro-fibrotic, apoptosis-resistant fibroblasts in IPF promotes progressive fibrosis and may have a role in other diseases, if these resistant cells are selected for as a consequence of treatment...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29789542/rnf25-promotes-gefitinib-resistance-in-egfr-mutant-nsclc-cells-by-inducing-nf-%C3%AE%C2%BAb-mediated-erk-reactivation
#4
Jung Hee Cho, Yeon-Mi You, Young Il Yeom, Dong Chul Lee, Bo-Kyung Kim, Misun Won, Byoung Chul Cho, Minho Kang, Seulki Park, Suk-Jin Yang, Jang Seong Kim, Jung-Ae Kim, Kyung Chan Park
Non-small cell lung cancer (NSCLC) patients with EGFR mutations initially respond well to EGFR tyrosine kinase inhibitors (TKIs) but eventually exhibit acquired or innate resistance to the therapies typically due to gene mutations, such as EGFR T790M mutation or a second mutation in the downstream pathways of EGFR. Importantly, a significant portion of NSCLC patients shows TKI resistance without any known mechanisms, calling more comprehensive studies to reveal the underlying mechanisms. Here, we investigated a synthetic lethality with gefitinib using a genome-wide RNAi screen in TKI-resistant EGFR-mutant NSCLC cells, and identified RNF25 as a novel factor related to gefitinib resistance...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29789534/the-novel-klf4-plac8-signaling-pathway-regulates-lung-cancer-growth
#5
Yunlu Jia, Xiaogang Ying, Jichun Zhou, Yongxia Chen, Xiao Luo, Shudu Xie, Qin Chuan Wang, Wenxian Hu, Linbo Wang
Accumulating evidence suggests that placenta-specific 8 (PLAC8) plays an important role in normal cellular process and human diseases, including multiple types of human tumors, and its role is highly relied upon in cellular and physiologic contexts. However, there are no reports on its expression profile and biological roles during lung cancer development. In the current study, both the clinical implications and biological effects of PLAC8 in lung cancer (LC) progression were investigated, and we identified and described the novel Krüppel-like factor 4 (KLF4)/PLAC8 regulatory pathway in cancer progression...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29788781/purines-and-triazolo-4-3-e-purines-containing-pyrazole-moiety-as-potential-anticancer-and-antioxidant-agents
#6
Omaima G Shaaban, Heba A Abd El Razik, Shams El-Dine A Shams El-Dine, Fawzia A Ashour, Alaa A El-Tombary, Ola S Afifi, Marwa M Abu-Serie
AIM: Targeting apoptosis regulators such as caspases aiming at inducing apoptosis is an attractive strategy in cancer therapy. MATERIALS & METHODS: 8-Substituted purine incorporating pyrazole moiety were designed, synthesized and evaluated for their anticancer and antioxidant activities. RESULTS: Compounds 7a and 8a displayed potent and selective anticancer activity against lung cancer A549 cell line with low cytotoxicity on peripheral blood mononuclear normal cells...
May 23, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29786614/a-novel-optimization-framework-for-vmat-with-dynamic-gantry-couch-rotation
#7
Qihui Lyu, Victoria Y Yu, Dan Ruan, Ryan Neph, Daniel O'Connor, Ke Sheng
Existing Volumetric Modulated Arc Therapy (VMAT) optimization using coplanar arcs is highly efficient but usually dosimetrically inferior to intensity modulated radiation therapy (IMRT) with optimized non-coplanar beams. To achieve both dosimetric quality and delivery efficiency, we proposed in this study, a novel integrated optimization method for non-coplanar VMAT (4πVMAT). 4πVMAT with Direct Aperture Optimization (DAO) was achieved by utilizing a least square dose fidelity objective, along with an anisotropic total variation term for regularizing the fluence smoothness, a single segment term for imposing simple apertures, and a group sparsity term for selecting beam angles...
May 22, 2018: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/29784736/targeted-therapy-for-patients-with-metastatic-non-small-cell-lung-cancer
#8
Karen L Reckamp
Molecular testing is recommended for initial diagnosis in patients with non-small cell lung cancer (NSCLC), according to the updated NCCN Guidelines, because targeted therapies are available that can improve patient outcomes. Targeted therapies are currently approved for EGFR mutations, ALK and ROS1 gene rearrangements, and BRAF mutations, with the list of emerging "actionable" targets growing. The 2018 NCCN Guidelines for NSCLC incorporate new therapies, including the EGFR tyrosine kinase inhibitor osimertinib and the ALK inhibitor alectinib, as first-line preferences...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29782570/egfr-targeted-therapy-for-lung-cancer-are-we-almost-there
#9
EDITORIAL
Giulio Metro
No abstract text is available yet for this article.
April 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29781034/specific-inhibitor-of-notch%C3%A2-3-enhances-the-sensitivity-of-nsclc-cells-to-gemcitabine
#10
Bi-Dan Hu, Jia Guo, Yuan-Zi Ye, Ting Du, Chun-Song Cheng, Qian Jiang, Ruo-Nan Liu, Yan-Bei Zhang
Notch‑3 is a receptor of the Notch signaling pathway and plays an important role in regulating self‑renewal, differentiation and apoptosis in cancer cells. Overexpression of Notch‑3 has been proved to be associated with resistance to gemcitabine (GEM) and poor patient prognosis for various malignant tumors. In the present study, two non‑small cell lung cancer (NSCLC) cell lines, H1299 and A549, were induced with GEM for two months and then were treated with various concentrations of a Notch signaling blocker, N‑[N‑(3,5‑difluorophenacetyl)‑L‑alanyl]‑S‑phenylglycine t‑butyl ester (DAPT), with the goal of reducing expression of Notch intracellular domain 3 (NICD3)...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29780635/liquid-biopsy-for-lung-cancer-early-detection
#11
REVIEW
Mariacarmela Santarpia, Alessia Liguori, Alessandro D'Aveni, Niki Karachaliou, Maria Gonzalez-Cao, Maria Grazia Daffinà, Chiara Lazzari, Giuseppe Altavilla, Rafael Rosell
Molecularly targeted therapies and immune checkpoint inhibitors have markedly improved the therapeutic management of advanced lung cancer. However, it still remains the leading cause of cancer-related mortality worldwide, with disease stage at diagnosis representing the main prognostic factor. Detection of lung cancer at an earlier stage of disease, potentially susceptible of curative resection, can be critical to improve patients survival. Low-dose computed tomography (LDCT) screening of high-risk patients has been demonstrated to reduce mortality from lung cancer, but can be also associated with high false-positive rate, thus often resulting in unnecessary interventions for patients...
April 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29780256/the-utilization-of-next-generation-sequencing-to-detect-somatic-mutations-and-predict-clinical-prognosis-of-chinese-non-small-cell-lung-cancer-patients
#12
Liming Cao, Long Long, Min Li, Huaping Yang, Pengbo Deng, Xinru Mao, Jianxing Xiang, Bing Li, Tengfei Zhang, Chengping Hu
Purpose: The development of next-generation sequencing (NGS) has revolutionized the understanding of oncogenesis of multiple types of cancer, including non-small cell lung cancer (NSCLC). However, there has been some debate over the utility of NGS for predicting patient prognosis and determining molecular targeted therapy. Therefore, we sought to demonstrate the numerous applications of NGS in the prognostic predictions and treatment of NSCLC patients. Materials and methods: We performed NGS on either liquid or tissue tumor biopsies obtained from 53 NSCLC patients...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29779975/design-and-synthesis-of-a-series-of-bioavailable-fatty-acid-synthase-fasn-kr-domain-inhibitors-for-cancer-therapy
#13
Tianbao Lu, Carsten Schubert, Maxwell D Cummings, Gilles Bignan, Peter J Connolly, Karine Smans, Donald Ludovici, Michael H Parker, Christophe Meyer, Christian Rocaboy, Richard Alexander, Bruce Grasberger, Sabine De Breucker, Norbert Esser, Erwin Fraiponts, Ron Gilissen, Boudewijn Janssens, Danielle Peeters, Luc Van Nuffel, Peter Vermeulen, James Bischoff, Lieven Meerpoel
We designed and synthesized a new series of fatty acid synthase (FASN) inhibitors with potential utility for the treatment of cancer. Extensive SAR studies led to highly active FASN inhibitors with good cellular activity and oral bioavailability, exemplified by compound 34. Compound 34 is a potent inhibitor of human FASN (IC50  = 28 nM) that effectively inhibits proliferation of A2780 ovarian cells (IC50  = 13 nM) in lipid-reduced serum (LRS). This cellular activity can be rescued by addition of palmitate, consistent with an on-target effect...
May 8, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29778566/lung-squamous-cell-carcinoma-cells-express-non-canonically-glycosylated-igg-that-activates-integrin-fak-signaling
#14
Jingshu Tang, Jingxuan Zhang, Yang Liu, Qinyuan Liao, Jing Huang, Zihan Geng, Weiyan Xu, Zhengzuo Sheng, Gregory Lee, Youhui Zhang, Jinfeng Chen, Liang Zhang, Xiaoyan Qiu
It is increasingly recognized that many human carcinomas express immunoglobulin (Ig) molecules that are distinct from B-cell-derived Ig and play important roles in cancer initiation, progression, and metastasis. However, the molecular mechanisms underlying the functions of cancer-derived Ig remain elusive. Here, we report that lung squamous cell carcinoma (LSCC) cells frequently express high levels of cancer IgG (CIgG) that is specifically recognized by a monoclonal antibody RP215. RP215 recognizes CIgG via a novel epitope that involves an N-glycan modification at a non-consensus site within the CH 1 domain...
May 17, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29777906/reduced-rar-%C3%AE-gene-expression-in-benzo-a-pyrene-induced-lung-cancer-mice-is-upregulated-by-dotap-lipo-atra-treatment
#15
S Viswanathan, V M Berlin Grace
Molecular targeted therapy for specific genes is an emerging research. Retinoic Acid Receptor (RAR-β) is a key tumor suppressor which is found to be lost drastically during much cancer progression. We hence, analyzed the expression level of RAR-β gene during B(a)P induced lung cancer development in mice and studied the lung cancer targeted action of All Trans Retinoic Acid (ATRA) in DOTAP liposomal formulation. The effect of its treatment on lung cancer was determined by histopathological analysis. RAR-β gene expression was assessed by RT-PCR and qPCR...
May 16, 2018: Gene
https://www.readbyqxmd.com/read/29777004/development-of-a-novel-spect-tracer-to-image-c-met-expression-in-non-small-cell-lung-cancer-in-a-human-tumor-xenograft
#16
Zhaoguo Han, Yadi Xiao, Kai Wang, Ji Yan, Zunyu Xiao, Fang Fang, Zhongnan Jin, Yang Liu, Xilin Sun, Baozhong Shen
Rationale: Elevated expression of the c-Met receptor plays a crucial role in cancers. In non-small cell lung cancer (NSCLC), aberrant activation of c-Met signaling pathway contributes to tumorigenesis and cancer progression, and may mediate acquired resistance to epidermal growth factor receptor-targeted therapy. c-Met is therefore emerging as a promising therapeutic target for treating NSCLC, and the methods for noninvasive in vivo assessment of c-Met expression will improve NSCLC treatment and diagnosis. Methods: A new peptide-based (cMBP) radiotracer targeting c-Met, 99m Tc-hydrazine nicotinamide (HYNIC)-cMBP, was developed for single photon emission computed tomography (SPECT) imaging...
May 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29776963/combined-vegf-and-pd-l1-blockade-displays-synergistic-treatment-effects-in-an-autochthonous-mouse-model-of-small-cell-lung-cancer
#17
Lydia Meder, Philipp Schuldt, Martin Thelen, Anna Schmitt, Felix Dietlein, Sebastian Klein, Sven Borchmann, Kerstin Wennhold, Ignacija Vlasic, Sebastian Oberbeck, Richard Riedel, Alexandra Florin, Kristina Golfmann, Hans Anton Schlößer, Margarete Odenthal, Reinhard Büttner, Juergen Wolf, Michael Hallek, Marco Herling, Michael von Bergwelt-Baildon, Hans Christian Reinhardt, Roland T Ullrich
Small cell lung cancer (SCLC) represents the most aggressive pulmonary neoplasm and is often diagnosed at late stage with limited survival, despite combined chemotherapies. We show in an autochthonous mouse model of SCLC that combined anti-VEGF/anti-PD-L1 targeted therapy synergistically improves treatment outcome compared to anti-PD-L1 and anti-VEGF monotherapy. Mice treated with anti-PD-L1 alone relapsed after 3 weeks and were associated with a tumor-associated PD-1/TIM-3 double positive exhausted T cell phenotype...
May 18, 2018: Cancer Research
https://www.readbyqxmd.com/read/29774063/dual-target-gene-therapy-to-eml4-alk-nsclc-by-a-gold-nanoshell-based-system
#18
Siwen Li, Yuxi Liu, Yalan Rui, Liping Tang, Samuel Achilefu, Yueqing Gu
Although EML4-ALK transforming fusion gene is represented in only 8% of non-small cell lung cancer (NSCLC) cases, its expression is partly responsive for the failure of current NSCLC treatments. Preventing secondary mutation of the ALK protein through direct gene manipulation could overcome NSCLC drug resistance. Method: In this study, we developed a gold nanoshell (HAuNs) drug carrier for delivery and selective photo-thermal release of genes that target ALK and microRNA-301 in NSCLC. Additionally, the densely-coated nanoshell adsorbed high amounts of the positively-charged anticancer drug doxorubicin (DOX), generating an exciting multidimensional treatment strategy that includes gene-, thermal- and chemo- therapy...
2018: Theranostics
https://www.readbyqxmd.com/read/29774061/immunotherapy-in-non-metastatic-non-small-cell-lung-cancer-can-the-benefits-of-stage-iv-therapy-be-translated-into-earlier-stages
#19
REVIEW
Griet Deslypere, Dorothée Gullentops, Els Wauters, Johan Vansteenkiste
Over the last decade, several steps forward in the treatment of patients with stage IV non-small cell lung cancer (NCSLC) were made. Examples are the use of pemetrexed, pemetrexed maintenance therapy, or bevacizumab for patients with nonsquamous NSCLC. A big leap forward was the use of tyrosine kinase inhibitors in patients selected on the basis of an activating oncogene, such as epidermal growth factor receptor ( EGFR ) activating mutations or anaplastic lymphoma kinase ( ALK ) translocations. However, all of these achievements could not be translated into survival benefits when studied in randomized controlled trials in patients with nonmetastatic NSCLC...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29773994/biological-roles-of-aberrantly-expressed-glycosphingolipids-and-related-enzymes-in-human-cancer-development-and-progression
#20
REVIEW
Dinghao Zhuo, Xiang Li, Feng Guan
Glycosphingolipids (GSLs), which consist of a hydrophobic ceramide backbone and a hydrophilic carbohydrate residue, are an important type of glycolipid expressed in surface membranes of all animal cells. GSLs play essential roles in maintenance of plasma membrane stability, in regulation of numerous cellular processes (including adhesion, proliferation, apoptosis, and recognition), and in modulation of signal transduction pathways. GSLs have traditionally been classified as ganglio-series, lacto-series, or globo-series on the basis of their diverse types of oligosaccharide chains...
2018: Frontiers in Physiology
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