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https://www.readbyqxmd.com/read/29348831/aberrant-expression-of-mir-21-mir-376c-and-mir-145-and-their-target-host-genes-in-merkel-cell-polyomavirus-positive-non-small-cell-lung-cancer
#1
Ismini Lasithiotaki, Eliza Tsitoura, Anastasios Koutsopoulos, Eleni Lagoudaki, Chara Koutoulaki, George Pitsidianakis, Demetrios A Spandidos, Nikolaos M Siafakas, George Sourvinos, Katerina M Antoniou
Merkel Cell Polyoma Virus (MCPyV) infection has been associated with non-small cell lung cancer (NSCLC). Viruses can manipulate cellular miRNAs or have a profound impact on cellular miRNA expression to control host regulatory pathways. In this study, we evaluated the expression profiles of cancer-associated and virally affected host microRNAs miR-21, miR-145, miR-146a, miR-155, miR-302c, miR-367 and miR-376c in a series of NSCLC tissue samples as well as in samples from "healthy" sites, distant from the tumour region that were either positive or negative for MCPyV DNA...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348459/distinct-dependencies-on-receptor-tyrosine-kinases-in-the-regulation-of-mapk-signaling-between-braf-v600e-and-non-v600e-mutant-lung-cancers
#2
Hiroshi Kotani, Yuta Adachi, Hidenori Kitai, Shuta Tomida, Hideaki Bando, Anthony C Faber, Takayuki Yoshino, Dominic C Voon, Seiji Yano, Hiromichi Ebi
BRAF is one of the most frequently mutated genes across a number of different cancers, with the best-characterized mutation being V600E. Despite the successes of treating BRAF mutant V600E lung cancer with BRAF pathway inhibitors, treatment strategies targeting tumors with non-V600E mutations are yet to be established. We studied cellular signaling differences between lung cancers with different BRAF mutations and determined their sensitivities to BRAF pathway inhibitors. Here, we observed that MEK inhibition induced feedback activation of the receptor tyrosine kinase (RTK) EGFR, and in some cases the RTK FGFR, resulting in transient suppression of ERK phosphorylation in BRAF non-V600E, but not BRAF V600E, mutant cells...
January 19, 2018: Oncogene
https://www.readbyqxmd.com/read/29334371/cooperative-targeting-of-melanoma-heterogeneity-with-an-axl-antibody-drug-conjugate-and-braf-mek-inhibitors
#3
Julia Boshuizen, Louise A Koopman, Oscar Krijgsman, Aida Shahrabi, Elke Gresnigt- van den Heuvel, Maarten A Ligtenberg, David W Vredevoogd, Kristel Kemper, Thomas Kuilman, Ji-Ying Song, Nora Pencheva, Jens Thing Mortensen, Marnix Geukes Foppen, Elisa A Rozeman, Christian U Blank, Maarten L Janmaat, David Satijn, Esther C W Breij, Daniel S Peeper, Paul W H I Parren
Intratumor heterogeneity is a key factor contributing to therapeutic failure and, hence, cancer lethality. Heterogeneous tumors show partial therapy responses, allowing for the emergence of drug-resistant clones that often express high levels of the receptor tyrosine kinase AXL. In melanoma, AXL-high cells are resistant to MAPK pathway inhibitors, whereas AXL-low cells are sensitive to these inhibitors, rationalizing a differential therapeutic approach. We developed an antibody-drug conjugate, AXL-107-MMAE, comprising a human AXL antibody linked to the microtubule-disrupting agent monomethyl auristatin E...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29331646/progress-in-the-management-of-advanced-thoracic-malignancies-in-2017
#4
REVIEW
Roberto Ferrara, Laura Mezquita, Benjamin Besse
The treatment paradigm of non-small cell lung cancer (NSCLC) underwent a major revolution during the course of 2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in response and overall survival (OS) both in unselected pretreated patients and in untreated patients with PD-L1 expression ≥50%. Furthermore, compelling preliminary results were reported for new combinations of anti-PD-1/PD-L1 agents with chemotherapy or anti-CTLA4 inhibitors. The success of the ICIs appeared to extend to patients with small cell lung cancer (SCLC), mesothelioma or thymic tumors...
January 10, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29322935/classifying-cancer-genome-aberrations-by-their-mutually-exclusive-effects-on-transcription
#5
Jonathan B Dayton, Stephen R Piccolo
BACKGROUND: Malignant tumors are typically caused by a conglomeration of genomic aberrations-including point mutations, small insertions, small deletions, and large copy-number variations. In some cases, specific chemotherapies and targeted drug treatments are effective against tumors that harbor certain genomic aberrations. However, predictive aberrations (biomarkers) have not been identified for many tumor types and treatments. One way to address this problem is to examine the downstream, transcriptional effects of genomic aberrations and to identify characteristic patterns...
December 21, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/29320776/v600e-braf-versus-non-v600e-braf-mutated-lung-adenocarcinomas-cytomorphology-histology-coexistence-of-other-driver-mutations-and-patient-characteristics
#6
Kevan J Salimian, Roghayeh Fazeli, Gang Zheng, David Ettinger, Zahra Maleki
OBJECTIVES: We analyzed the morphologic features and clinical characteristics of lung adenocarcinomas (ACAs) harboring mutated BRAF. STUDY DESIGN: A review of the histology/cytology of BRAF-mutated lung ACAs was performed at the Johns Hopkins Hospital from January 1, 2013, to January 1, 2015. Patient demographics, clinical history, and ACA morphology were assessed. RESULTS: Thirty-six cases were identified with a median age of 66 years (range 44-87), 58% (21/36) were female, and 94% (34/36) were current or former smokers...
January 11, 2018: Acta Cytologica
https://www.readbyqxmd.com/read/29312770/development-of-pulmonary-langerhans-cell-histiocytosis-in-a-patient-with-established-adenocarcinoma-of-the-lung
#7
Or Kalchiem-Dekel, Adina Paulk, Seth J Kligerman, Allen P Burke, Nirav G Shah, Renee K Dixon
Newly-appearing lung nodules on surveillance imaging in patients with pre-existing lung cancer can present a diagnostic dilemma when attempting to differentiate between metastatic disease, infection, and other inflammatory conditions. Here we report a case of an EGFR-/ALK-/BRAF+ metastatic adenocarcinoma patient who underwent lung biopsy for evaluation of upper-lobe predominant lung nodules revealed to represent pulmonary Langerhans cell histiocytosis (PLCH). The patient was a heavy smoker and admitted to increase her smoking habit after initially learning about her diagnosis with lung cancer...
December 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29312762/ciliated-muconodular-papillary-tumor-of-the-lung-harboring-braf-v600e-mutation-and-p16ink4a-overexpression-without-proliferative-activity-may-represent-an-example-of-oncogene-induced-senescence
#8
Lucia Kim, Young Sam Kim, Jin Soo Lee, Suk Jin Choi, In Suh Park, Jee Young Han, Joon Mee Kim, Young Chae Chu
Ciliated muconodular papillary tumor (CMPT) is a rare peripheral lung tumor that shows puzzling histologic features encompassing metaplastic and neoplastic nature. This type of tumor is occasionally misdiagnosed as lung adenocarcinoma clinically and pathologically, and its pathogenic mechanism has not been well characterized. We experienced a case of CMPT in a 73-year-old male and performed targeted deep sequencing to characterize its molecular features. The tumor was an ill-defined, subpleural, and non-endobronchial nodule showing glandular and papillary proliferation of mucous cells, ciliated columnar cells, and basal cells without any cytologic atypia...
December 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29306909/detection-of-egfr-kras-and-braf-mutations-in-metastatic-cells-from-cerebrospinal-fluid
#9
Diane Frankel, Isabelle Nanni-Metellus, Andrée Robaglia-Schlupp, Pascale Tomasini, Julien Guinde, Fabrice Barlesi, Philippe Astoul, L'Houcine Ouafik, Florent Amatore, Véronique Secq, Elise Kaspi, Patrice Roll
BACKGROUND: In lung adenocarcinoma, molecular profiling of actionable genes has become essential to set up targeted therapies. However, the feasibility and the relevance of molecular profiling from the cerebrospinal fluid (CSF) in the context of meningeal metastasis have been poorly assessed. METHODS: We selected patients with stage IV lung adenocarcinoma harbouring metastatic cells in the CSF after cytological analysis. Seven samples from six patients were eligible for molecular testing of epidermal growth factor receptor (EGFR), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue (KRAS), v-Raf murine sarcoma viral oncogene homologue B1 (BRAF) and human epidermal growth factor receptor 2 (HER2) mutations using quantitative polymerase chain reaction (PCR) high-resolution melting curve analysis and Sanger sequencing after DNA extraction from the cell pellets of the CSF...
January 8, 2018: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29304903/locked-nucleic-acid-technology-for-highly-sensitive-detection-of-somatic-mutations-in-cancer
#10
Takayuki Ishige, Sakae Itoga, Kazuyuki Matsushita
The molecular diagnosis of the cancer mutational status is essential for modern clinical laboratory medicine. Mutations in EGFR, KRAS, BRAF, and PIK3CA genes are widely analyzed in solid tumors such as lung cancer, colorectal cancer, breast cancer, and melanoma. The allele-specific polymerase chain reaction, high-resolution melting, and Sanger sequencing are used for detecting and identifying gene mutations in many clinical laboratories. The locked nucleic acid (LNA) is a class of nucleic acid analogs that contain a methylene bridge connecting the 2' oxygen and 4' carbon in the ribose moiety...
2018: Advances in Clinical Chemistry
https://www.readbyqxmd.com/read/29295962/rational-approaches-for-combination-therapy-strategies-targeting-the-map-kinase-pathway-in-solid-tumors
#11
Anthony W Tolcher, Wei Peng, Emiliano Calvo
Molecular characterization of oncogenic mutations within genes in the MAPK and PI3K/AKT/mTOR pathways has led to the rational development of targeted therapies. Combining BRAF and MEK inhibitors to target two steps in the MAPK pathway (vertical inhibition) is now standard of care in advanced-stage melanoma harboring BRAF V600 mutation. Encouraging results have been seen in several tumor types with the same mutation, including BRAF V600-mutant non-small cell lung cancer. Yet similar results in other tumors, such as colorectal cancer, have not been observed, highlighting the unique nature of different tumors...
January 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29295876/rapid-clinical-and-radiographic-response-with-combined-dabrafenib-and-trametinib-in-adults-with-braf-mutated-high-grade-glioma
#12
Tanner M Johanns, Cole J Ferguson, Patrick M Grierson, Sonika Dahiya, George Ansstas
BRAF V600E mutations have been successfully treated with targeted therapy in melanoma, non-small cell lung cancer, and thyroid cancer. Interestingly, these mutations have also been identified in a subset of pediatric and adult brain tumors, with several cases reportedly responding to targeted therapy. However, these reports have been limited to single-agent BRAF inhibitor therapy and recurrent disease. Herein, we report dramatic clinical and radiographic responses to combination dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) in 2 adults with high-grade gliomas (HGGs), with 1 patient treated in the first-line setting...
January 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29261000/successful-treatment-using-apatinib-with-or-without-docetaxel-in-heavily-pretreated-advanced-non-squamous-non-small-cell-lung-cancer-a-case-report-and-literature-review
#13
Fengying Wu, Shijia Zhang, Guanghui Gao, Jing Zhao, Shengxiang Ren, Caicun Zhou
Although targeted therapy directed toward driver mutations has produced a significant efficacy benefit for patients with non-small cell lung cancer (NSCLC), many patients do not possess mutations associated with the approved targeted drugs. Angiogenic agents play an important role in the therapeutic strategy for advanced NSCLC. Apatinib is a novel tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor-2. A phase II clinical trial demonstrated the survival benefit of apatinib monotherapy in advanced NSCLC...
December 20, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29259016/oncogenic-ras-induced-perinuclear-signaling-complexes-requiring-ksr1-regulate-signal-transmission-to-downstream-targets
#14
Sandip K Basu, Sook Lee, Jacqueline Salotti, Srikanta Basu, Krisada Sakchaisri, Zhen Xiao, Vijay Walia, Christopher J Westlake, Deborah K Morrison, Peter F Johnson
The precise characteristics that distinguish normal and oncogenic RAS signaling remain obscure. Here we show that oncogenic RAS and BRAF induce perinuclear re-localization of several RAS pathway proteins, including the kinases CK2 and p-ERK1/2 and the signaling scaffold KSR1. This spatial reorganization requires endocytosis, the kinase activities of MEK-ERK and CK2, and the presence of KSR1. CK2α co-localizes with KSR1 and Rab11, a marker of recycling endosomes, whereas p-ERK associates predominantly with a distinct KSR1-positive endosomal population...
December 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/29249325/outcomes-in-patients-with-non-small-cell-lung-cancer-and-acquired-thr790met-mutation-treated-with-osimertinib-a-genomic-study
#15
Chia-Chi Lin, Jin-Yuan Shih, Chong-Jen Yu, Chao-Chi Ho, Wei-Yu Liao, Jih-Hsing Lee, Tzu-Hsiu Tsai, Kang-Yi Su, Min-Shu Hsieh, Yih-Leong Chang, Ya-Ying Bai, Derek De-Rui Huang, Kenneth S Thress, James Chih-Hsin Yang
BACKGROUND: Osimertinib is approved for the treatment of non-small-cell lung cancer in patients who develop the EGFR Thr790Met mutation after treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs). We assessed outcomes in patients with non-small-cell lung cancer and the EGFR Thr790Met mutation who were treated with osimertinib, a third-generation EGFR TKI, after previous treatment failure with one or more other EGFR TKIs. METHODS: Eligible patients had been enrolled at one centre in the AURA study, had shown resistance to a previous EGFR TKI, and had EGFR-activating mutations and acquired Thr790Met mutation detectable in tumour tissue or plasma...
December 14, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29248665/a-case-of-a-primary-lung-cancer-comprised-of-adenocarcinoma-and-atypical-carcinoid-tumor-with-both-components-harboring-braf-p-v600e-mutation
#16
Andrea M Olofson, Laura J Tafe
Mixed morphology lung tumors are rare; this is the second report of a combined NSCLC and atypical carcinoid tumor. Next generation sequencing was performed on both histologically distinct patterns which identified that both components harbored a BRAF p.V600E mutation. Molecular studies inform our knowledge of the biology and aid in treatment decisions for mixed morphology lung cancers.
December 14, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29230121/leptomeningeal-disease-and-the-evolving-role-of-molecular-targeted-therapy-and-immunotherapy
#17
REVIEW
Katharine Hall Thomas, Robert A Ramirez
Background: Leptomeningeal disease (LMD) is a complication that results from solid tumor metastasis. Prognosis is extremely poor. As therapeutic options for solid tumors improve, the rate of LMD continues to increase. Until recently, treatment has been limited to radiation therapy, intrathecal chemotherapy, and systemic chemotherapy, with an overall survival of 2-3 months. Targeted molecular therapy and immunotherapies are promising new options for increasing overall survival and clinical improvement; however, optimal clinical management remains unknown...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/29228562/clinical-mutational-profiling-of-1006-lung-cancers-by-next-generation-sequencing
#18
Peter B Illei, Deborah Belchis, Li-Hui Tseng, Doreen Nguyen, Federico De Marchi, Lisa Haley, Stacy Riel, Katie Beierl, Gang Zheng, Julie R Brahmer, Frederic B Askin, Christopher D Gocke, James R Eshleman, Patrick M Forde, Ming-Tseh Lin
Analysis of lung adenocarcinomas for actionable mutations has become standard of care. Here, we report our experience using next generation sequencing (NGS) to examine AKT1, BRAF, EGFR, ERBB2, KRAS, NRAS, and PIK3CA genes in 1006 non-small cell lung cancers in a clinical diagnostic setting. NGS demonstrated high sensitivity. Among 760 mutations detected, the variant allele frequency (VAF) was 2-5% in 33 (4.3%) mutations and 2-10% in 101 (13%) mutations. A single bioinformatics pipeline using Torrent Variant Caller, however, missed a variety of EGFR mutations...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227119/-molecular-pathology-of-lung-cancer-in-routine-diagnostic-practice-2017-update
#19
Radoslav Matěj, Zdeněk Rohan, Kristýna Němejcová, Pavel Dundr
The group of non-small cell lung carcinomas includes tumors that are variable at the clinical, histopathological and molecular levels. Advances in the understanding of molecular pathology of lung adenocarcinomas in particular led to changes in their histopathological classification and treatment. Patients diagnosed with lung adenocarcinoma harboring specific mutations benefit from the administration of specific targeted therapy. Analysis of EGFR gene mutations and ALK rearrangement in lung adenocarcinomas are already routinely performed and are closely related to the indication for the administration of tyrosinkinase inhibitors...
2017: Ceskoslovenská Patologie
https://www.readbyqxmd.com/read/29222807/long-non-coding-rna-expression-in-bladder-cancer
#20
REVIEW
Mohammad Taheri, Mir Davood Omrani, Soudeh Ghafouri-Fard
The advent of novel high-throughput sequencing methods has facilitated identification of non-coding RNAs with fundamental roles in cellular biological and pathological conditions. A group of these consisting of at least 200 nucleotides are called long non-coding RNAs (lncRNAs). Their participation in the pathogenesis of cancer has been highlighted in recent years. Bladder cancer, one of the most prevalent cancers worldwide, exhibits altered expression levels of several lncRNAs. Several in vitro and in vivo studies have assessed the effects of silencing RNAs on cancer cell phenotypes and in vivo tumor growth...
December 8, 2017: Biophysical Reviews
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