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Targeted therapies lung cancer

Huixing Deng, Geng Qianqian, Ji Ting, Yang Aimin
microRNAs (miRNAs) have been implicated to play critical roles in non-small celllung cancer (NSCLC) progression and participate in the regulation of drug resistance during cancer chemotherapy. However, the underlying molecular mechanism of how miR-539 modulates the chemosensitivity to cisplatin (DDP) in NSCLC cells remains largely unknown. In this study, we found that miR-539 was significantly downregulated in DDP-resistant cell lines (A549/DDP and H1299/DDP). Overexpression of miR-539 enhanced the sensitivity of DDP-resistant NSCLC cells to DDP by suppressing cell proliferation, causing cell cycle arrest, inducing apoptosis, repressing invasion and migration...
July 16, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Robert Roskoski
The Ras-Raf-MEK-ERK signal transduction cascade is arguably the most important oncogenic pathway in human cancers. Ras-GTP promotes the formation of active homodimers or heterodimers of A-Raf, B-Raf, and C-Raf by an intricate process. These enzymes are protein-serine/threonine kinases that catalyze the phosphorylation and activation of MEK1 and MEK2 which, in turn, catalyze the phosphorylation and activation of ERK1 and ERK2. The latter catalyze the regulatory phosphorylation of dozens of cytosolic and nuclear proteins...
August 14, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Eiichi Sasaki, Daisuke Nishikawa, Nobuhiro Hanai, Yasuhisa Hasegawa, Yasushi Yatabe
AIMS: Molecular targeted therapy against EGFR kinase domain mutations has been successfully established for lung cancer. These mutations now have also been reported in head and neck tumours, particularly in inverted sinonasal papillomas (ISPs). The aim of this study was to clarify the spectrum of EGFR mutations in head and neck squamous cell carcinomas and papillomas. METHODS AND RESULTS: We examined EGFR mutations in 288 head and neck squamous cell carcinomas and 58 head and neck papillomas or polyps...
August 17, 2018: Histopathology
Dorra Amor, Sébastien Goutal, Solène Marie, Fabien Caillé, Martin Bauer, Oliver Langer, Sylvain Auvity, Nicolas Tournier
BACKGROUND: Erlotinib is an epidermal growth factor receptor (EGFR)-targeting tyrosine kinase inhibitor approved for treatment of non-small cell lung cancer. The wide inter-individual pharmacokinetic (PK) variability of erlotinib may impact treatment outcome and/or toxicity. Recent in vivo studies reported a nonlinear uptake transport of erlotinib into the liver, suggesting carrier-mediated system(s) to mediate its hepatobiliary clearance. Erlotinib has been identified in vitro as a substrate of organic anion-transporting polypeptide (OATP) transporters which expression does not restrict to hepatocytes and may impact the tissue uptake of erlotinib in vivo...
August 16, 2018: EJNMMI Research
Xinpeng Li, Naxin Yuan, Lingdan Lin, Lixia Yin, Yiqing Qu
Non-small cell lung cancer (NSCLC) is the most frequent type of human lung cancer; lung cancer is responsible for the highest rates of cancer-associated mortality in the world. Cysteine-rich angiogenic inducer-61 (CYR-61) has been identified as a tumorigenesis-, development- and metastasis-related gene, and is reported to enhance proliferation, migration and invasion through hepatocyte growth factor (HGF)-induced scattering and the metastasis-inducing HGF/Met signaling pathway in tumor cells and xenograft models...
August 2018: Experimental and Therapeutic Medicine
Laila Al-Eryani, Samantha F Jenkins, Vanessa A States, Jianmin Pan, Janine C Malone, Shesh N Rai, Susan Galandiuk, Ashok K Giri, J Christopher States
Arsenic, a naturally occurring element, contaminates the drinking water of over 200 million people globally. Chronic arsenic exposure causes multiple cancers including those originating from skin, lung and bladder, and is associated with liver, kidney, and prostate cancers. Skin is the primary target organ for arsenic toxicity; chronic toxicity initially manifests as non-malignant hyperkeratoses (HK) and subsequently advances to malignant lesions, including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC)...
2018: PloS One
Meijia Wu, Ting Huang, Juan Wang, Ping Chen, Wanwan Mi, Yuanyuan Ying, Hangli Wang, Dandan Zhao, Shengwu Huang
BACKGROUND: Lung cancer is one of the most important diseases threatening human health, and targeted therapy has become the main research direction. This work, therefore, aimed to develop cyclic arginine-glycine-aspartic (RGD) and octa-arginine (R8) peptide-modified ergosterol (ERG)-combined cisplatin (diamminedichloridoplatinum(II) [DDP]) liposomes (LIP) as a drug delivery system. METHODS: Soybean phospholipids (SPC) and cholesterol (Chol) were selected to prepare different LIPs: ERG-loaded LIP (ERG-LIP), DDP and ERG-LIP (DDP/ERG-LIP), R8 peptide-modified DDP and ERG-LIP (R8-DDP/ERG-LIP), and cyclic RGD and R8-DDP/ERG-LIP (RGD/R8-DDP/ERG-LIP)...
August 2018: Medicine (Baltimore)
Rakesh Kumar Singh, Abul Kalam Najmi
OBJECTIVE: The primary focus of this review is to highlight the current and emerging pro-inflammatory role of MK2 kinase signaling in p38MAPK pathway and to provide a detailed evaluation on the prospects of MK2 inhibition with special emphasis on the etiology of chronic inflammatory airway diseases, such as asthma, idiopathic pulmonary fibrosis, lung cancer, acute lung injury and acute respiratory distress syndrome. BACKGROUND: Mitogen-activated protein kinase-activated protein kinase 2 (MK2) is a serine-threonine kinase downstream to p38MAPK and is activated directly by stress and inflammatory signal through p38 phosphorylation...
August 16, 2018: Current Drug Targets
D E Meyers, P M Bryan, S Banerji, D G Morris
Lung cancer is the leading cause of cancer-specific death among Canadians, with non-small-cell lung cancer (nsclc) being the most common histologic variant. Despite advances in the understanding of the molecular biology of nsclc, the survival rate for this malignancy is still poor. It is now understood that, to evade detection and immune clearance, nsclc tumours overexpress the immunosuppressive checkpoint protein programmed death ligand 1 (PD-L1). Inhibiting the PD-1/PD-L1 axis with monoclonal antibodies has significantly changed the treatment landscape in nsclc during the last 5 years...
August 2018: Current Oncology
Anida Hasanovic, Isabelle Mus-Veteau
One of the crucial challenges in the clinical management of cancer is resistance to chemotherapeutics. Multidrug resistance (MDR) has been intensively studied, and one of the most prominent mechanisms underlying MDR is overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) transporters. Despite research efforts to develop compounds that inhibit the efflux activity of ABC transporters and thereby increase classical chemotherapy efficacy, to date, the Food and Drug Administration (FDA) has not approved the use of any ABC transporter inhibitors due to toxicity issues...
August 14, 2018: Cells
Kei Ichiji, Yusuke Yoshida, Noriyasu Homma, Xiaoyong Zhang, Ivo Bukovsky, Yoshihiro Takai, Makoto Yoshizawa
In radiation therapy, for accurate radiation dose delivery to a target tumor and reduction of the extra exposure of normal tissues, real-time tumor tracking is an important technique typically for a lung cancer treatment since the lung tumor moves with patient's respiration. To observe the tumor motion in real time, X-ray fluoroscopic devices can be employed, and various tracking techniques have been proposed to track the tumor. However, development of an accurate and fast-tracking method for clinical use is still a challenging task since the obscureness can cause the decreased tracking accuracy and additional processing time for improving the accuracy...
August 15, 2018: Physics in Medicine and Biology
George Oche Ambrose, Olanrewaju John Afees, Nwufoh Chika Nwamaka, Nzikahyel Simon, Adebo Adeola Oluwaseun, Tosin Soyinka, Alakanse Suleiman Oluwaseun, Seyi Bankole
The life-threatening sides effect of the current EGFR mutant inhibitors (drugs) such as the eruption of rash which can be seen on the face, chest, back and even the trunk, diarrhea, nausea, vomiting, anorexia and stomatitis, necessitates the discovery of new potent and safe compounds as a chemo-therapeutic measure against lung cancer. Approximately about 10% of patients with Non-small cell lung cancer (NSCLC) in the US and about 35% in East Asia have tumor associated EGFR. These mutations occur within EGFR exon 18-21, which encodes a portion of the EGFR kinase domain and enables researchers to identify compounds that only recognizes and binds to the cancer cells...
2018: Bioinformation
Lining Huang, Xingming Jiang, Zhidong Wang, Xiangyu Zhong, Sheng Tai, Yunfu Cui
OBJECTIVES: Long non-coding RNAs (lncRNAs), a group of transcripts with length greater than 200 nucleotides, have been involved in multiple pathophysiological processes of the human body, especially in tumorigenesis and progression of cancers. The aberrant expression of lncRNAs processes crucial functions involved in proliferation, apoptosis and metastatic capacity of cancers. Recent studies have revealed that small nucleolar RNA host gene 1 (SNHG1), a long non-coding RNA transcribed from UHG, was located in chromosome 11...
August 2, 2018: Pathology, Research and Practice
Shang-Gin Wu, Yi-Nan Liu, Chong-Jen Yu, James Chih-Hsin Yang, Jin-Yuan Shih
Young lung cancer patients have several distinct characteristics. However, there are limited epidemiological data of genetic abnormalities in this population. We conducted a prospective cohort study to delineate the various oncogenic driver mutations of lung adenocarcinoma in young Asian patients. We consecutively collected malignant pleural effusions (MPEs) from lung adenocarcinoma patients. RNA was extracted from MPEs for mutation analysis by reverse transcription-polymerase chain reaction and direct sequencing...
August 14, 2018: Genes, Chromosomes & Cancer
Fabio Gomes, Rebecca Tay, Jaseela Chiramel, Raffaele Califano
Lung cancer is predominantly a disease of the elderly. This subgroup of patients poses many challenges and an appropriate geriatric assessment is crucial for treatment personalisation in order to reduce the risk of over- or under-treatment. Whilst cytotoxic chemotherapy has been the backbone of advanced non-small cell lung cancer (NSCLC) treatment for decades, the development of targeted agents for driver mutations such as EGFR, ALK, BRAF and ROS1 has changed the treatment paradigm and natural history of this disease...
August 14, 2018: Drugs & Aging
Kevin M Sullivan, Heidi L Kenerson, Venu G Pillarisetty, Kimberly J Riehle, Raymond S Yeung
With the widespread adoption of molecular profiling in clinical oncology practice, many physicians are faced with making therapeutic decisions based upon isolated genomic alterations. For example, epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) are effective in EGFR-mutant non-small cell lung cancers (NSCLC) while anti-EGFR monoclonal antibodies are ineffective in Ras-mutant colorectal cancers. The matching of mutations with drugs aimed at their respective gene products represents the current state of "precision" oncology...
July 2018: Annals of Translational Medicine
Emma Maria Dunne, Ian Mark Fraser, Mitchell Liu
Stereotactic body radiation therapy (SBRT) also referred to as stereotactic ablative radiotherapy (SABR), is a technique which has emerged over the past two decades due to improvements in radiation technology. Unlike conventional external beam radiotherapy (cEBRT) which traditionally delivers radiation in small doses [approximately 2 Gray (Gy) per fraction] over several weeks, SBRT, typically delivered in one to eight fractions, is a technique whereby potentially ablative doses of radiotherapy (usually 7.5-20 Gy per fraction) can be delivered with steeper dose gradients and sub millimetre precision, minimising risk to surrounding normal tissues...
July 2018: Annals of Translational Medicine
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
In the version of this article originally published, information regarding several funding sources was omitted from the Acknowledgements section. The following sentences should have been included: "This work was supported by the generous philanthropic contributions to The University of Texas MD Anderson Lung Cancer Moon Shots Program, the UT Lung SPORE 5 P50 CA07090, and the MD Anderson Cancer Center Support Grant P30CA01667. V.P is supported by R01CA155196-01A1 from the National Cancer Institute." Also, reference 18 was incorrect...
August 13, 2018: Nature Medicine
Sharon R Pine
Lung cancer is the leading cause of cancer deaths among men and women. Gamma-secretase inhibitors, a class of small molecule compounds that target the Notch pathway, have been tested to treat non-small cell lung cancer (NSCLC) in pre-clinical and clinical trials. Although ɣ-secretase inhibitors elicit a response in some tumors as single agents and sensitize NSCLC to cytotoxic and targeted therapies, they have not yet been approved for NSCLC therapy. We discuss our recently published pre-clinical study using the ɣ-secretase inhibitor AL101, formerly BMS906024, on cell lines and PDX models of NSCLC, primarily lung adenocarcinoma...
August 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Daniel Sappington, Scott Helms, Eric Siegel, Rosalind B Penney, Susanne Jeffus, Teka Bartter, Thaddeus Bartter, Gunnar Boysen
BACKGROUND: Treatment of lung cancer is evolving from the use of cytotoxic drugs to drugs that interrupt pathways specific to a malignancy. The field of metabolomics has promise with respect to identification of tumor-specific processes and therapeutic targets, but to date has yielded inconsistent data in patients with lung cancer. Lymph nodes are often aspirated in the process of evaluating lung cancer, as malignant cells in lymph nodes are used for diagnosis and staging. We hypothesized that fluids from lymph node aspirates contains tumor-specific metabolites and are a suitable source for defining the metabolomic phenotype of lung cancers...
2018: Cancer Treatment and Research Communications
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