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https://www.readbyqxmd.com/read/29331646/progress-in-the-management-of-advanced-thoracic-malignancies-in-2017
#1
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/29329131/alk-gene-fusions-in-epithelioid-fibrous-histiocytoma-a-study-of-14-cases-with-new-histopathological-findings
#2
Dmitry V Kazakov, Liubov Kyrpychova, Petr Martinek, Petr Grossmann, Petr Steiner, Tomas Vanecek, Michal Pavlovsky, Vladimir Bencik, Michael Michal, Michal Michal
Previous studies showed that ALK is often positive in epithelioid fibrous histiocytoma (EFH). Two cases of EFH with ALK gene fusions have been recorded. Our objective was to study a series of EFH to present histopathological variations of EFH, identify novel ALK gene fusions, and determine whether there is a correlation between histopathological features and particular gene. We investigated 14 cases of EFH, all ALK immunopositive. The cases were assessed histopathologically as well as for ALK and TFE-3 rearrangements using FISH and ALK gene fusions using next-generation sequencing...
January 11, 2018: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/29327718/epithelioid-fibrous-histiocytoma-molecular-characterization-of-alk-fusion-partners-in-23-cases
#3
Brendan C Dickson, David Swanson, George S Charames, Christopher Dm Fletcher, Jason L Hornick
Epithelioid fibrous histiocytoma is a rare and distinctive cutaneous neoplasm. Most cases harbor ALK rearrangement and show ALK overexpression, which distinguish this neoplasm from conventional cutaneous fibrous histiocytoma and variants. SQSTM1 and VCL have previously been shown to partner with ALK in one case each of epithelioid fibrous histiocytoma. The purpose of this study was to examine a large cohort of epithelioid fibrous histiocytomas by next-generation sequencing to characterize the nature and prevalence of ALK fusion partners...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29327716/genomic-heterogeneity-of-alk-fusion-breakpoints-in-non-small-cell-lung-cancer
#4
Jason N Rosenbaum, Ryan Bloom, Jason T Forys, Jeff Hiken, Jon R Armstrong, Julie Branson, Samantha McNulty, Priya D Velu, Kymberlie Pepin, Haley Abel, Catherine E Cottrell, John D Pfeifer, Shashikant Kulkarni, Ramaswamy Govindan, Eric Q Konnick, Christina M Lockwood, Eric J Duncavage
In lung adenocarcinoma, canonical EML4-ALK inversion results in a fusion protein with a constitutively active ALK kinase domain. Evidence of ALK rearrangement occurs in a minority (2-7%) of lung adenocarcinoma, and only ~60% of these patients will respond to targeted ALK inhibition by drugs such as crizotinib and ceritinib. Clinically, targeted anti-ALK therapy is often initiated based on evidence of an ALK genomic rearrangement detected by fluorescence in situ hybridization (FISH) of interphase cells in formalin-fixed, paraffin-embedded tissue sections...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29325035/amplicon-based-next-generation-sequencing-of-plasma-cell-free-dna-for-detection-of-driver-and-resistance-mutations-in-advanced-non-small-cell-lung-cancer
#5
N Guibert, Y Hu, N Feeney, Y Kuang, V Plagnol, G Jones, K Howarth, J F Beeler, C P Paweletz, G R Oxnard
Background: Genomic analysis of plasma cell-free DNA is transforming lung cancer care, however available assays are limited by cost, turnaround time, and imperfect accuracy. Here we study amplicon-based plasma next-generation sequencing (NGS), rather than hybrid-capture-based plasma NGS, hypothesizing this would allow sensitive detection and monitoring of driver and resistance mutations in advanced non-small cell lung cancer (NSCLC). Methods: Plasma samples from patients with NSCLC and a known targetable genotype (EGFR, ALK/ROS1 and other rare genotypes) were collected while on therapy and analyzed, blinded to tumor genotype...
January 9, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29323742/a-molecular-dynamics-investigation-into-the-mechanisms-of-alectinib-resistance-of-three-alk-mutants
#6
Muyang He, Weikang Li, Qingchuan Zheng, Hongxing Zhang
Alectinib, a highly selective next-genetation anaplastic lymphoma kinase (ALK) inhibitor, has demonstrated promising antitumor activity in patients with ALK-positive non-small cell lung carcinomas (NSCLC). However, the therapeutic benefits of alectinib is inescapably hampered by the development of acquired resistant mutations in ALK. Despite the availability of ample experimental mutagenesis data, the molecular origin and the structural motifs under alectinib binding affinity deficiencies are still ambiguous...
January 11, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29323068/story-of-survival-in-anaplastic-large-cell-lymphoma-sometimes-more-than-the-anaplastic-lymphoma-kinase-status-an-evaluation-of-pathologic-prognostic-factors-in-102-cases
#7
Komal Agrawal, Tanuja Shet, Epari Sridhar, Suhas Dhende, Manju Sengar, Brijesh Arora, Siddhartha Laskar, Sumeet Gujral, Hari Menon, Shripad Banavali
INTRODUCTION: Systemic anaplastic large cell lymphoma (ALCL) accounts for 5%-10% of adult non Hodgkin's lymphoma (NHL) and 10%-30% of childhood NHL. Owing to significant differences in survival and gene expression profile, current WHO classifies ALCL into two distinct entities as anaplastic lymphoma receptor tyrosine kinase (ALK) positive and ALK negative ALCL with ALK expression by tumour as a good prognostic indicator. However, in our institute which is a cancer referral institute, our preliminary experience was that even ALK positive tumours did not fare well as compared to ALK- negative ALCL...
October 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/29321932/acute-onset-of-ulcerative-colitis-during-chemoradiotherapy-for-anaplastic-lymphoma-kinase-positive-lung-adenocarcinoma
#8
Kohei Fujita, Yoshinori Mizumoto, Koki Moriyoshi, Norio Araki, Tadashi Mio
We report a case of acute onset of ulcerative colitis (UC) during chemoradiotherapy in a patient with anaplastic lymphoma kinase (ALK)-positive lung adenocarcinoma. A 46-year-old male patient with an abnormal chest shadow was referred to our hospital. He was diagnosed with lung adenocarcinoma, clinical stage T1aN3M0 and stage IIIB. Concurrent chemoradiotherapy was selected for his initial therapy. After two cycles of cisplatin and vinorelbine administration, he experienced persistent diarrhoea and anorexia...
February 2018: Respirology Case Reports
https://www.readbyqxmd.com/read/29321660/activated-alk-signals-through-the-erk-etv5-ret-pathway-to-drive-neuroblastoma-oncogenesis
#9
Lucille Lopez-Delisle, Cécile Pierre-Eugène, Caroline Louis-Brennetot, Didier Surdez, Virginie Raynal, Sylvain Baulande, Valentina Boeva, Sandrine Grossetête-Lalami, Valérie Combaret, Michel Peuchmaur, Olivier Delattre, Isabelle Janoueix-Lerosey
Activating mutations of the ALK receptor occur in a subset of neuroblastoma tumors. We previously demonstrated that Alk mutations cooperate with MYCN overexpression to induce neuroblastoma in mice and identified Ret as being strongly upregulated in MYCN/Alkmut tumors. By a genetic approach in vivo, we now document an oncogenic cooperation between activated Ret and MYCN overexpression in neuroblastoma formation. We show that MYCN/RetM919T tumors exhibit histological features and expression profiles close to MYCN/Alkmut tumors...
January 11, 2018: Oncogene
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
#10
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/29318404/does-alk-rearrangement-predict-favorable-response-to-the-therapy-of-bevacizumab-plus-pemetrexed-in-advanced-non-small-cell-lung-cancer-case-report-and-literature-review
#11
Zhichao Liu, Youting Bao, Butuo Li, Xindong Sun, Linlin Wang
BACKGROUND: Advanced ALK-rearranged non-small cell lung cancer (NSCLC) patients will develop acquired resistance after anaplastic lymphoma kinase (ALK) inhibitors therapies. Vascular endothelial growth factor-A (VEGF-A) production and tumor vessel formation were found to be more significantly enriched in ALK-rearrangement NSCLC than that in epidermal growth factor receptor or Kirsten rat sarcoma viral oncogene mutated NSCLC. However, the correlation between ALK rearrangement and the efficacy of bevacizumab (a recombinant humanized IgG1 monoclonal antibody targeting VEGF-A) was still elusive...
January 9, 2018: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/29317835/real-world-usage-and-clinical-outcomes-of-alectinib-among-post-crizotinib-progression-anaplastic-lymphoma-kinase-positive-non-small-cell-lung-cancer-patients-in-the-usa
#12
Marco D DiBonaventura, William Wong, Bijal Shah-Manek, Mathias Schulz
Background: Alectinib is an approved treatment for anaplastic lymphoma kinase (ALK)-positive patients with advanced non-small-cell lung cancer. Despite positive supporting clinical data, there is a lack of real-world information on the usage and patient outcomes of those treated with alectinib post-crizotinib progression. Methods: Participating oncologists (N=95) in the USA were recruited from an online physician panel to participate in a retrospective patient chart review...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29317532/alkals-are-in-vivo-ligands-for-alk-family-receptor-tyrosine-kinases-in-the-neural-crest-and-derived-cells
#13
Andrey Fadeev, Patricia Mendoza-Garcia, Uwe Irion, Jikui Guan, Kathrin Pfeifer, Stephanie Wiessner, Fabrizio Serluca, Ajeet Pratap Singh, Christiane Nüsslein-Volhard, Ruth H Palmer
Mutations in anaplastic lymphoma kinase (ALK) are implicated in somatic and familial neuroblastoma, a pediatric tumor of neural crest-derived tissues. Recently, biochemical analyses have identified secreted small ALKAL proteins (FAM150, AUG) as potential ligands for human ALK and the related leukocyte tyrosine kinase (LTK). In the zebrafish Danio rerio, DrLtk, which is similar to human ALK in sequence and domain structure, controls the development of iridophores, neural crest-derived pigment cells. Hence, the zebrafish system allows studying Alk/Ltk and Alkals involvement in neural crest regulation in vivo...
January 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29317515/intratumoural-heterogeneity-may-hinder-precision-medicine-strategies-in-patients-with-clear-cell-renal-cell-carcinoma
#14
Maria Rosaria Raspollini, Ilaria Montagnani, Rodolfo Montironi, Francesca Castiglione, Guido Martignoni, Liang Cheng, Antonio Lopez-Beltran
Clear cell renal cell carcinoma (ccRCC) is an heterogeneous tumour at architectural, cellular and molecular level, a reason why the 2014 International Society of Urological Pathology consensus recommended wide sampling of RCC masses to include at least 1 block/cm of tumour together with perpendicular sections of the tumour/perinephric fat interface and the tumour/renal sinus interface. Intratumoural molecular heterogeneity may be a limitation at the moment of defining precision medicine strategies based on gene mutation status...
January 9, 2018: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29317428/small-cell-transformation-of-alk-rearranged-non-small-cell-adenocarcinoma-of-the-lung
#15
Agnes Balla, Kenneth J Hampel, Farrah Khan, Dara L Aisner, Nikoletta Sidiropoulos
Anaplastic lymphoma kinase (ALK) gene rearrangements are present in approximately 5% of non-small-cell lung cancers (NSCLCs). These rearrangements occur because of a chromosomal inversion within the short arm of chromosome 2, which results in the formation of the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion oncogene. While NSCLC transformation to SCLC is a rare phenomenon described in EGFR mutant cancers primarily after treatment with targeted therapy, it is exceedingly rare in ALK rearranged adenocarcinomas (Toyokawa et al...
January 9, 2018: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/29317165/discovery-of-novel-2-substituted-4-phenoxypyridine-derivatives-as-potential-antitumor-agents
#16
Yongli Duan, Shan Xu, Hehua Xiong, Linxiao Wang, Bingbing Zhao, Ping Wang, Caolin Wang, Yiqing Peng, Shifan Cai, Rong Luo, Pengwu Zheng, Qidong Tang
A series of 2-substituted-4-phenoxypyridine derivatives were designed, synthesized, and evaluated for their antiproliferative activity against 4 cancer cell lines (A549, HT-29, H460, and U87MG) in vitro. Most compounds showed moderate to excellent potency. Nine tyrosine kinases (c-Met, Flt-3, ALK, VEGFR-2, VEGFR-3, PDGFR-α, PDGFR-β, c-Kit, and EGFR) were used to evaluate the inhibitory activities with the most promising analogue 39, which showed the Flt-3/c-Met IC50 values of 2.18/2.61 nM. Structure-activity relationship studies indicated that n-Pr served as R1 group showed a higher preference, and stronger mono-EWGs on the phenyl ring (such as R2 = 4-F) was benefited to the potency...
December 29, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29315860/nanoparticle-cell-interaction-a-cell-mechanics-perspective
#17
REVIEW
Dedy Septiadi, Federica Crippa, Thomas Lee Moore, Barbara Rothen-Rutishauser, Alke Petri-Fink
Progress in the field of nanoparticles has enabled the rapid development of multiple products and technologies; however, some nanoparticles can pose both a threat to the environment and human health. To enable their safe implementation, a comprehensive knowledge of nanoparticles and their biological interactions is needed. In vitro and in vivo toxicity tests have been considered the gold standard to evaluate nanoparticle safety, but it is becoming necessary to understand the impact of nanosystems on cell mechanics...
January 9, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29315286/alk-inhibitors-in-non-small-cell-lung-cancer-how-many-are-needed-and-how-should-they-be-sequenced
#18
Alice T Shaw
No abstract text is available yet for this article.
December 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29312770/development-of-pulmonary-langerhans-cell-histiocytosis-in-a-patient-with-established-adenocarcinoma-of-the-lung
#19
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/29312610/inhibitor-repurposing-reveals-alk-ltk-fgfr-ret-and-trk-kinases-as-the-targets-of-azd1480
#20
Iva Gudernova, Lukas Balek, Miroslav Varecha, Jana Fialova Kucerova, Michaela Kunova Bosakova, Bohumil Fafilek, Veronika Palusova, Stjepan Uldrijan, Lukas Trantirek, Pavel Krejci
Many tyrosine kinase inhibitors (TKIs) have failed to reach human use due to insufficient activity in clinical trials. However, the failed TKIs may still benefit patients if their other kinase targets are identified by providing treatment focused on syndromes driven by these kinases. Here, we searched for novel targets of AZD1480, an inhibitor of JAK2 kinase that recently failed phase two cancer clinical trials due to a lack of activity. Twenty seven human receptor tyrosine kinases (RTKs) and 153 of their disease-associated mutants were in-cell profiled for activity in the presence of AZD1480 using a newly developed RTK plasmid library...
December 12, 2017: Oncotarget
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