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Kerryn M Taylor, Roxanne Wheeler, Nimisha Singh, Dalene Vosloo, David W Ray, Paula Sommer
Small cell lung cancer (SCLC) is a highly aggressive, predominantly cigarette smoke-induced tumour with poor prognosis. The glucocorticoid receptor (GR), a SCLC tumour suppressor gene, is typically reduced in SCLC. We now show that SCLC cells express high levels of DNA methyltransferase 1 (DNMT1) which accumulates at the GR promoter. DNMT1 expression is further increased by exposure to the tobacco carcinogen NNK. In the untransformed human lung fibroblast cell line, MRC-5, short term NNK treatment decreases GRα mRNA and protein expression due to accumulation of DNMT1 at the GR promoter...
March 20, 2018: Scientific Reports
Matthew J Farrell, Jehan B Yahya, Catherine Degnin, Yiyi Chen, John M Holland, Mark A Henderson, Jerry J Jaboin, Matthew M Harkenrider, Charles R Thomas, Timur Mitin
PURPOSE: Prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (LS-SCLC) is considered the standard of care. Meta-analysis of 7 clinical trials indicates a survival benefit to PCI, but all of these trials were conducted in the pre-magnetic resonance imaging (MRI) era. Therefore, routine brain imaging with MRI before PCI-as recommended by National Comprehensive Cancer Network guidelines-is not directly supported by the evidence. Current US practice patterns for patients with LS-SCLC are unknown...
February 23, 2018: Clinical Lung Cancer
Hongyang Lu, Bo Chen, Jing Qin, Fajun Xie, Na Han, Zhiyu Huang
The present study describes the case of a 48-year-old man who was diagnosed with lung adenocarcinoma with an epidermal growth factor receptor (EGFR) 21 L858R mutation. The patient received surgery and adjuvant chemotherapy. When multiple lung metastases appeared, icotinib was administered. Following resistance to icotinib, biopsy by endobroncheal ultrasonography for a right lung hilar lymph node revealed transformation to a neuroendocrine morphology. Neuron-specific enolase (NSE) levels were elevated, accompanied with disease progression following transformation to the neuroendocrine morphology...
April 2018: Oncology Letters
Midori Tanaka, Hidenobu Ishii, Hayato Moribuchi, Yoshiko Naito, Norikazu Matsuo, Masayuki Nakamura, Takaaki Tokito, Koichi Azuma, Kazuhiko Yamada, Tomoaki Hoshino
Small-cell lung cancer (SCLC) combined with epidermal growth factor receptor (EGFR) mutations is extremely rare, and standard chemotherapeutic strategies have not yet been established. In the present study, we report a case of a 67-year-old man who presented with combined SCLC with EGFR mutation (exon 19 deletion). Systemic chemotherapy with cisplatin and irinotecan was initiated as first-line chemotherapy, and computed tomography findings revealed tumor shrinkage after two cycles of chemotherapy. However, after the third cycle of the treatment, disease progression was observed including the appearance of pleural and pericardial effusion...
March 15, 2018: Investigational New Drugs
Zhong Ni, Xiting Wang, Tianchen Zhang, Linlin Li, Jianxue Li
Small cell lung cancer (SCLC) is the subtype of lung cancer with the highest degree of malignancy and the lowest degree of differentiation. The purpose of this study was to investigate the molecular mechanisms of SCLC using bioinformatics analysis, and to provide new ideas for the early diagnosis and targeted therapy of SCLC. Microarray data were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) in SCLC were compared with the normal lung samples and identified. Gene Ontology (GO) function and pathway analysis of DEGs was performed through the DAVID database...
April 2018: Experimental and Therapeutic Medicine
Antonio Rossi, Rebecca Tay, Jaseela Chiramel, Arsela Prelaj, Raffaele Califano
Small-cell lung cancer (SCLC) is a very aggressive disease characterized by a high response rate to first-line chemotherapy, but most patients relapse within 1 year with disappointing results to second-line treatments. Chemotherapy has reached a plateau of effectiveness and new therapeutic strategies are needed to change the natural history of SCLC. Areas covered: This review will focus on the current results and the future development of the therapeutic approaches for the treatment of SCLC. Expert commentary: Immunotherapy is becoming a new frontier for the management of SCLC with preliminary interesting results...
March 15, 2018: Expert Review of Anticancer Therapy
Patrizia Ciammella, Giorgia Timon, Alessio Bruni, Davide Franceschini, Paolo Borghetti, Nicolò Giaj-Levra, Carlo Greco, Vieri Scotti, Marco Trovo
INTRODUCTION: Radiation therapy plays an important role in the management of SCLC both in curative and palliative setting, however, conflicting data from clinical trials incite debate over the appropriate use of radiation therapy regarding prophylactic cranial irradiation (PCI) and/or thoracic consolidative in extensive-stage SCLC (ES-SCLC). This survey is conducted to evaluate the current pattern of care among Italian radiation oncologists. METHODS: In June 2016, all Italian radiation oncologists were invited to a web-based survey...
March 13, 2018: La Radiologia Medica
Anna F Farago, Florence K Keane
Small cell lung cancer (SCLC) is an aggressive high-grade neuroendocrine carcinoma. Despite over 30 years of clinical research, little progress has been made in the management of SCLC, and outcomes remain poor. Here, we review the current clinical standards for management of SCLC and the data supporting these strategies.
February 2018: Translational Lung Cancer Research
Triparna Sen, Carl M Gay, Lauren Averett Byers
Small cell lung cancer (SCLC) is an aggressive malignancy that accounts for 14% of all lung cancer diagnoses. Despite decades of active research, treatment options for SCLC are limited and resistance to the few Food and Drug Administration (FDA) approved therapies develops rapidly. With no approved targeted agents to date, new therapeutic strategies are desperately needed. SCLC is characterized by high mutation burden, ubiquitous loss of TP53 and RB1, mutually exclusive amplification of MYC family members, thereby, high genomic instability...
February 2018: Translational Lung Cancer Research
Wei Zhang, Luc Girard, Yu-An Zhang, Tomohiro Haruki, Mahboubeh Papari-Zareei, Victor Stastny, Hans K Ghayee, Karel Pacak, Trudy G Oliver, John D Minna, Adi F Gazdar
Background: Small cell lung cancer (SCLC) is a deadly, high grade neuroendocrine (NE) tumor without recognized morphologic heterogeneity. However, over 30 years ago we described a SCLC subtype with "variant" morphology which did not express some NE markers and exhibited more aggressive growth. Methods: To quantitate NE properties of SCLCs, we developed a 50-gene expression-based NE score that could be applied to human SCLC tumors and cell lines, and genetically engineered mouse (GEM) models...
February 2018: Translational Lung Cancer Research
Yan Ting Shue, Jing Shan Lim, Julien Sage
Small cell lung carcinoma (SCLC) is a fast-growing, highly metastatic form of lung cancer. A major difference between SCLC and other forms of lung cancer is that SCLC tumors often respond well to chemotherapy initially; unfortunately, resistant tumors rapidly recur. In addition, despite a large number of clinical trials with a variety of therapeutic agents, little progress has been achieved in the past three decades in improving the survival of SCLC patients. These clinical observations indicate that SCLC tumors have a high degree of plasticity and rapid adaptability to changes in growth conditions...
February 2018: Translational Lung Cancer Research
Dong-Wook Kim, Keun-Cheol Kim, Kee-Beom Kim, Colin T Dunn, Kwon-Sik Park
The discovery of recurrent alterations in genes encoding transcription regulators and chromatin modifiers is one of the most important recent developments in the study of the small cell lung cancer (SCLC) genome. With advances in models and analytical methods, the field of SCLC biology has seen remarkable progress in understanding the deregulated transcription networks linked to the tumor development and malignant progression. This review will discuss recent discoveries on the roles of RB and P53 family of tumor suppressors and MYC family of oncogenes in tumor initiation and development...
February 2018: Translational Lung Cancer Research
Carine Ghassan Richa, Khadija Jamal Saad, Georges Habib Halabi, Elie Mekhael Gharios, Fadi Louis Nasr, Marie Tanios Merheb
The objective of this study is to report three cases of paraneoplastic or ectopic Cushing syndrome, which is a rare phenomenon of the adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome. Three cases are reported in respect of clinical presentation, diagnosis and treatment in addition to relevant literature review. The results showed that ectopic ACTH secretion can be associated with different types of neoplasm most common of which are bronchial carcinoid tumors, which are slow-growing, well-differentiated neoplasms with a favorable prognosis and small-cell lung cancer, which are poorly differentiated tumors with a poor outcome...
2018: Endocrinology, Diabetes & Metabolism Case Reports
Julie George, Vonn Walter, Martin Peifer, Ludmil B Alexandrov, Danila Seidel, Frauke Leenders, Lukas Maas, Christian Müller, Ilona Dahmen, Tiffany M Delhomme, Maude Ardin, Noemie Leblay, Graham Byrnes, Ruping Sun, Aurélien De Reynies, Anne McLeer-Florin, Graziella Bosco, Florian Malchers, Roopika Menon, Janine Altmüller, Christian Becker, Peter Nürnberg, Viktor Achter, Ulrich Lang, Peter M Schneider, Magdalena Bogus, Matthew G Soloway, Matthew D Wilkerson, Yupeng Cun, James D McKay, Denis Moro-Sibilot, Christian G Brambilla, Sylvie Lantuejoul, Nicolas Lemaitre, Alex Soltermann, Walter Weder, Verena Tischler, Odd Terje Brustugun, Marius Lund-Iversen, Åslaug Helland, Steinar Solberg, Sascha Ansén, Gavin Wright, Benjamin Solomon, Luca Roz, Ugo Pastorino, Iver Petersen, Joachim H Clement, Jörg Sänger, Jürgen Wolf, Martin Vingron, Thomas Zander, Sven Perner, William D Travis, Stefan A Haas, Magali Olivier, Matthieu Foll, Reinhard Büttner, David Neil Hayes, Elisabeth Brambilla, Lynnette Fernandez-Cuesta, Roman K Thomas
Pulmonary large-cell neuroendocrine carcinomas (LCNECs) have similarities with other lung cancers, but their precise relationship has remained unclear. Here we perform a comprehensive genomic (n = 60) and transcriptomic (n = 69) analysis of 75 LCNECs and identify two molecular subgroups: "type I LCNECs" with bi-allelic TP53 and STK11/KEAP1 alterations (37%), and "type II LCNECs" enriched for bi-allelic inactivation of TP53 and RB1 (42%). Despite sharing genomic alterations with adenocarcinomas and squamous cell carcinomas, no transcriptional relationship was found; instead LCNECs form distinct transcriptional subgroups with closest similarity to SCLC...
March 13, 2018: Nature Communications
Mami Morita, Taku Sato, Miyuki Nomura, Yoshimi Sakamoto, Yui Inoue, Ryota Tanaka, Shigemi Ito, Koreyuki Kurosawa, Kazunori Yamaguchi, Yuki Sugiura, Hiroshi Takizaki, Yoji Yamashita, Ryuichi Katakura, Ikuro Sato, Masaaki Kawai, Yoshinori Okada, Hitomi Watanabe, Gen Kondoh, Shoko Matsumoto, Ayako Kishimoto, Miki Obata, Masaki Matsumoto, Tatsuro Fukuhara, Hozumi Motohashi, Makoto Suematsu, Masaaki Komatsu, Keiichi I Nakayama, Toshio Watanabe, Tomoyoshi Soga, Hiroshi Shima, Makoto Maemondo, Nobuhiro Tanuma
Expression of PKM2, which diverts glucose-derived carbon from catabolic to biosynthetic pathways, is a hallmark of cancer. However, PKM2 function in tumorigenesis remains controversial. Here, we show that, when expressed rather than PKM2, the PKM isoform PKM1 exhibits a tumor-promoting function in KRASG12D -induced or carcinogen-initiated mouse models or in some human cancers. Analysis of Pkm mutant mouse lines expressing specific PKM isoforms established that PKM1 boosts tumor growth cell intrinsically. PKM1 activated glucose catabolism and stimulated autophagy/mitophagy, favoring malignancy...
March 12, 2018: Cancer Cell
Xiaomeng Wan, Yuanzeng Min, Herdis Bludau, Andrew Keith, Sergei S Sheiko, Rainer Jordan, Andrew Z Wang, Marina Sokolsky-Papkov, Alexander V Kabanov
Nanoparticle-based systems for concurrent delivery of multiple drugs can improve outcomes of cancer treatments, but face challenges because of differential solubility and fairly low threshold for incorporation of many drugs. Here we demonstrate that this approach can be used to greatly improve the treatment outcomes of etoposide (ETO) and platinum drug combination ("EP/PE") therapy that is the backbone for treatment of prevalent and deadly small cell lung cancer (SCLC). A polymeric micelle system based on amphiphilic block copolymer poly(2-oxazoline)s (POx) poly(2-methyl-2-oxazoline-block-2-butyl-2-oxazoline-block-2-methyl-2-oxazoline) (P(MeOx-b-BuOx-b-MeOx) is used along with an alkylated cisplatin prodrug to enable co-formulation of EP/PE in a single high-capacity vehicle...
March 13, 2018: ACS Nano
Macy Liu
No abstract text is available yet for this article.
February 2018: Translational Lung Cancer Research
Dong-Wan Kim, Hoon-Gu Kim, Joo-Hang Kim, Keunchil Park, Hoon-Kyo Kim, Joung Soon Jang, Bong-Seog Kim, Jin-Hyoung Kang, Kyung Hee Lee, Sang-We Kim, Hun Mo Ryoo, Jin-Soo Kim, Ki Hyeong Lee, Jung Hye Kwon, Jin-Hyuk Choi, Sang Won Shin, Seokyung Hahn, Dae Seog Heo
Purpose: This randomized phase III study was designed to compare the efficacy and safety of irinotecan plus cisplatin (IP) over etoposide plus cisplatin (EP) in Korean patients with extensive-disease small-cell lung cancer (SCLC). Materials and Methods: Patients were randomly assigned to receive IP, composed of irinotecan 65 mg/m2 intravenously on days 1 and 8 + cisplatin 70 mg/m2 intravenously on day1 every 3 weeks, or EP, composed of etoposide 100 mg/m2 intravenously on days 1, 2, 3+cisplatin 70 mg/m2 intravenously on day 1, every 3 weeks for a maximum of six cycles, until disease progression, or until unacceptable toxicity occurred...
March 12, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Chi Hoon Maeng, Jae-Uk Song, Sung Ryul Shim, Jonghoo Lee
INTRODUCTION: The role of prophylactic cranial irradiation (PCI) is controversial in patients with extensive stage small cell lung cancer (ES-SCLC). The aim of this study was to determine the impact of PCI in these patients. METHODS: We performed a systematic review and meta-analysis in accordance with PRISMA guidelines. A systematic literature search was conducted in MEDLINE, EMBASE, and the Cochrane Central Register. The primary outcome was overall survival (OS)...
March 8, 2018: Journal of Thoracic Oncology
Yifeng Xia, Cheng Zhan, Mingxiang Feng, Mathias Leblanc, Eugene Ke, Narayana Yeddula, Inder M Verma
Small cell lung cancer (SCLC) is the most deadly subtype of lung cancer due to its dismal prognosis. We have developed a lentiviral vector-mediated SCLC mouse model and have explored the role of both the NF-κB and CREB families of transcription factors in this model. Surprisingly, induction of NF-κB activity, which promotes tumor progression in many cancer types including non-small cell lung carcinoma (NSCLC), is dispensable in SCLC. Instead, suppression of NF-κB activity in SCLC tumors moderately accelerated tumor development...
March 9, 2018: Molecular Cancer Research: MCR
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