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https://www.readbyqxmd.com/read/28534251/sequencing-of-alk-inhibitors-in-alk-non-small-cell-lung-cancer
#1
REVIEW
Shirish M Gadgeel
Major therapeutic advances have occurred over the last several years in the management of advanced ALK+ NSCLC patients. Crizotinib was the first agent approved for the management of ALK+ NSCLC patients after it demonstrated significantly greater clinical benefit compared to chemotherapy. Several next generation ALK inhibitors have demonstrated clinical benefit in patients with crizotinib refractory NSCLC patients including in the CNS. Based on available data, therapy with a next generation ALK inhibitor can be initiated following therapy with crizotinib without any assessment of the molecular mechanisms of resistance...
June 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28534101/evaluation-of-alk-gene-rearrangement-in-central-nervous-system-metastases-of-non-small-cell-lung-cancer-using-two-step-rt-pcr-technique
#2
M Nicoś, P Krawczyk, K Wojas-Krawczyk, A Bożyk, B Jarosz, M Sawicki, T Trojanowski, J Milanowski
PURPOSE: RT-PCR technique has showed a promising value as pre-screening method for detection of mRNA containing abnormal ALK sequences, but its sensitivity and specificity is still discussable. Previously, we determined the incidence of ALK rearrangement in CNS metastases of NSCLC using IHC and FISH methods. MATERIALS: We evaluated ALK gene rearrangement using two-step RT-PCR method with EML4-ALK Fusion Gene Detection Kit (Entrogen, USA). The studied group included 145 patients (45 females, 100 males) with CNS metastases of NSCLC and was heterogeneous in terms of histology and smoking status...
May 22, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28532546/-a-case-report-of-pulmonary-sarcomatoid-carcinoma-with-alk-rearrangement
#3
Yehong Miao, Lin Ling, Xiuqin Zhang, Jian'an Huang
No abstract text is available yet for this article.
May 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28529902/current-state-of-immunotherapy-for-non-small-cell-lung-cancer
#4
REVIEW
Jyoti Malhotra, Salma K Jabbour, Joseph Aisner
Lung cancer is the leading cause of cancer mortality and non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancers. Platinum-based doublet chemotherapy is the standard first-line treatment for metastatic NSCLC when genomic testing reveals no targetable alteration such as epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) or ROS1 translocation/re-arrangements. But, chemotherapy produces response rates ranging only between 15-30%. For patients whose disease progresses on first-line chemotherapy, second-line therapy historically consists of taxane-based salvage chemotherapy with a response rate of less than 25%...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28529640/lung-cancer-targeting-peptides-with-multi-subtype-indication-for-combinational-drug-delivery-and-molecular-imaging
#5
Yi-Hsuan Chi, Jong-Kai Hsiao, Ming-Huang Lin, Chen Chang, Chun-Hsin Lan, Han-Chung Wu
Lung cancer is the leading cause of cancer-related death worldwide. Most targeted drugs approved for lung cancer treatment are tyrosine kinase inhibitors (TKIs) directed against EGFR or ALK, and are used mainly for adenocarcinoma. At present, there is no effective or tailored targeting agent for large cell carcinoma (LCC) or small cell lung cancer (SCLC). Therefore, we aimed to identify targeting peptides with diagnostic and therapeutic utility that possess broad subtype specificity for SCLC and non-small cell lung cancer (NSCLC)...
2017: Theranostics
https://www.readbyqxmd.com/read/28528303/discovery-of-a-potent-dual-alk-and-egfr-t790m-inhibitor
#6
Jaebong Jang, Jung Beom Son, Ciric To, Magda Bahcall, So Young Kim, Seock Yong Kang, Mierzhati Mushajiang, Younho Lee, Pasi A Jänne, Hwan Geun Choi, Nathanael S Gray
The mutational activations of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) are validated oncogenic events and the targets of approved drugs to treat non-small cell lung cancer (NSCLC). Here we report highly potent dual small molecule inhibitors of both ALK and EGFR, particularly the T790M mutant which confers resistance to first generation EGFR inhibitors. Dual ALK/EGFR inhibitors may provide an efficient approach to prevent resistance that arises as a consequence of clinically reported reciprocal activation mechanisms...
May 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28526734/brigatinib-achieves-whole-body-and-intracranial-responses
#7
(no author information available yet)
Brigatinib is tolerable and has antitumor activity in crizotinib-resistant ALK-positive NSCLC.
May 19, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28522751/targeting-fbw7-as-a-strategy-to-overcome-resistance-to-targeted-therapy-in-non-small-cell-lung-cancer
#8
Mingxiang Ye, Yong Zhang, Xinxin Zhang, Jian-Bin Zhang, Pengyu Jing, Liang Cao, Nan Li, Xia Li, Libo Yao, Jian Zhang, Jian Zhang
Inhibition of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) signaling is highly effective in a subgroup of non-small cell lung cancer (NSCLC) patients with distinct clinicopathological features. However, resistance to EGFR and ALK inhibitors inevitably occurs, and the molecular mechanism underlying resistance is not fully understood. In this study, we report a PI3K/Akt- and MEK/Erk-independent resistance mechanism by which loss of the E3 ubiquitin ligase F-box and WD repeat domain containing 7 (FBW7α) leads to targeted therapy resistance via stabilization of anti-apoptotic protein MCL-1...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28522440/dusp22-and-tp63-rearrangements-predict-outcome-of-alk-negative-anaplastic-large-cell-lymphoma-a-danish-cohort-study
#9
Martin Bjerregård Pedersen, Stephen Jacques Hamilton-Dutoit, Knud Bendix, Rhett P Ketterling, Patrick P Bedroske, Ivy M Luoma, Christopher A Sattler, Rebecca L Boddicker, N Nora Bennani, Peter Nørgaard, Michael Boe Møller, Torben Steiniche, Francesco d'Amore, Andrew L Feldman
No abstract text is available yet for this article.
May 18, 2017: Blood
https://www.readbyqxmd.com/read/28521447/ct-guided-aspiration-lung-biopsy-for-egfr-and-alk-gene-mutation-analysis-of-lung-cancer
#10
Weisheng Lian, Yong Ouyang
The present study investigated the rates of detection and the positive rates of computed tomography (CT)-guided aspiration of lung biopsy for epidermal growth factor receptor (EGFR) gene and anaplastic lymphoma kinase (ALK) gene, and analyzed the relationship between gene mutation and clinical characteristics to improve the rate of related factors of gene detection. The clinical data and CT-guided aspiration biopsy specimen of 250 patients with lung cancer. Data showed that the rate of EGFR gene mutation was 41...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521285/arid1b-alterations-identify-aggressive-tumors-in-neuroblastoma
#11
Soo Hyun Lee, Jung-Sun Kim, Siyuan Zheng, Jason T Huse, Joon Seol Bae, Ji Won Lee, Keon Hee Yoo, Hong Hoe Koo, Sungkyu Kyung, Woong-Yang Park, Ki Woong Sung
Targeted panel sequencing was performed to determine molecular targets and biomarkers in 72 children with neuroblastoma. Frequent genetic alterations were detected in ALK (16.7%), BRCA1 (13.9%), ATM (12.5%), and PTCH1 (11.1%) in an 83-gene panel. Molecular targets for targeted therapy were identified in 16 of 72 patients (22.2%). Two-thirds of ALK mutations were known to increase sensitivity to ALK inhibitors. Sequence alterations in ARID1B were identified in 5 of 72 patients (6.9%). Four of five ARID1B alterations were detected in tumors of high-risk patients...
April 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28520828/targeted-therapy-as-an-alternative-to-whole-brain-radiotherapy-in-egfr-mutant-or-alk-positive-non-small-cell-lung-cancer-with-brain-metastases
#12
Pablo Martínez, Raymond H Mak, Geoffrey R Oxnard
Clinical Question: Is up-front whole-brain radiotherapy required to treat multiple brain metastases from non-small-cell lung cancer when highly active targeted therapies are available? Clinical Application: Patients with EGFR-mutant or ALK-positive non-small-cell lung cancer with brain metastases now have the potential to achieve a prolonged survival. Through use of highly active targeted therapies, whole-brain radiotherapy can be safely postponed, diminishing toxic effects that could impair quality of life...
May 18, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28517937/cellular-shuttles-monocytes-macrophages-exhibit-transendothelial-transport-of-nanoparticles-under-physiological-flow
#13
Thomas Moore, Daniel Hauser, Thomas Gruber, Barbara Rothen-Rutishauser, Marco Lattuada, Alke Petri-Fink, Ruth Lyck
A major hurdle in the development of biomedical nanoparticles (NP) is understanding how they interact with complex biological systems and navigate biological barriers to arrive at pathological targets. It is becoming increasingly evident that merely controlling particle physico-chemical properties may not be sufficient to mediate particle biodistribution in dynamic environments. Thus, researchers are increasingly turning towards more complex but likewise more physiological in vitro systems to study particle-cell/particle-system interactions...
May 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28516197/optimized-immunohistochemistry-using-the-d5f3-antibody-provides-a-reliable-test-for-identification-of-alk-positive-lung-adenocarcinomas
#14
Gian Luca Rampioni Vinciguerra, Stefania Scarpino, Benedetto Pini, Claudia Cippitelli, Flavio Fochetti, Luigi Ruco
We used optimized immunohistochemistry (IHC) with the D5F3 antibody for detection of tumours in a prospective study of 307 pulmonary adenocarcinomas. Cases positive by IHC (1+, 2+, 3+) were further investigated by fluorescent in situ hybridization (FISH). Of 307 cases, 22 (7.2%) were moderately intensely positive (2+/3+); 18 of these (82%) were also positive by FISH. Of the four IHC-positive/FISH-negative cases, one was unsuitable for FISH and three had abnormalities of the ALK gene. All cases with weak reactivity with D5F3 (1+) were FISH-negative...
May 17, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28516080/cutaneous-anaplastic-large-t-cell-lymphoma-with-invasion-of-the-central-nervous-system-a-case-report
#15
Hyun-Nam Seo, Jin-Ho Seo, Cheol-Young Lee, Jihye Song, Jong-Hyun Kim, Hyun-Woo Kim
Anaplastic large T-cell lymphoma (ALCL) encompasses different clinical entities that can be aggressive or localized. Scalp anaplastic lymphoma kinase (ALK)-negative ALCL is considered a localized lymphoma, and usually extends to the regional lymph nodes; intracranial invasion is rare. A 74-year-old woman was diagnosed with scalp ALK-negative ALCL, but did not exhibit invasion of the lymph nodes. Computed tomography and magnetic resonance imaging revealed intracranial masses with bony erosions. We treated the patient using CHOP chemotherapy and achieved short-term regression of the scalp and intracranial lesions...
April 2017: Brain Tumor Research and Treatment
https://www.readbyqxmd.com/read/28515245/biomarker-based-treatment-selection-in-non-small-cell-lung-cancer
#16
Wallace Akerley
Patients with non-small cell lung cancer must be tested for biomarkers. Currently, treatments directed against EGFR, ALK, and ROS1 mutations are standard of care. A number of emerging new targets and treatments are on the horizon.
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28515244/what-when-and-how-of-biomarker-testing-in-non-small-cell-lung-cancer
#17
Gregory L Riely
Biomarker testing is recommended for all patients diagnosed with non-small cell lung cancer. At a minimum, testing should include the mutations/fusions EGFR, ALK, ROS1, and the protein programmed death ligand-1 (PD-L1), because FDA-approved therapies are available for these alterations. Other actionable molecular findings include RET rearrangements, BRAF(V600E) mutations, and MET exon 14 alterations. If adequate testing was not performed at treatment initiation, molecular testing should be performed before administration of subsequent lines of therapy...
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28514931/lung-cancer-in-never-smokers-what-are-the-differences
#18
Margarida Dias, Rita Linhas, Sérgio Campainha, Sara Conde, Ana Barroso
INTRODUCTION: Characteristics of never-smokers with lung cancer are still not fully clarified. The aim of this study was to compare never-smokers and ever-smokers with non-small cell lung cancer (NSCLC) regarding patient and tumor characteristics. METHODS: All consecutive newly NSCLC patients with known smoking status diagnosed between 2011 and 2015 were included in this retrospective cohort study. Clinical, histological, and molecular characteristics were compared between ever-smokers and never-smokers...
July 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28514730/circulating-micrornas-as-novel-biomarkers-of-alk-positive-nonsmall-cell-lung-cancer-and-predictors-of-response-to-crizotinib-therapy
#19
Liang-Liang Li, Li-Li Qu, Han-Jiang Fu, Xiao-Fei Zheng, Chuan-Hao Tang, Xiao-Yan Li, Jian Chen, Wei-Xia Wang, Shao-Xing Yang, Lin Wang, Guan-Hua Zhao, Pan-Pan Lv, Min Zhang, Yang-Yang Lei, Hai-Feng Qin, Hong Wang, Hong-Jun Gao, Xiao-Qing Liu
Circulating microRNAs are potential diagnostic and predictive biomarkers, but have not been investigated for patients with anaplastic lymphoma kinase (ALK)-positive lung cancer. In this exploratory study, we sought to identify potential plasma biomarkers for ALK-positive non-small cell lung cancer (NSCLC). A microRNA microarray was used to select ALK-related microRNAs in ALK-positive NSCLC (n = 3), ALK-negative NSCLC (n = 3), and healthy subjects (n = 3). Plasma levels of 21 microRNAs were differentially expressed for ALK-positive and ALK-negative NSCLC, including 14 down-regulated and 7 up-regulated microRNAs...
April 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28513466/non-small-cell-lung-cancer-mutations-targeted-and-combination-therapy
#20
Justyna Kutkowska, Irena Porębska, Andrzej Rapak
Year after year, a growing number of cases of non-small cell lung cancer (NSCLC), mostly caused by smoking, have been noted. Most patients die because of the late detection of cancer and tumor resistance to treatment with cytostatics. Treatment of patients with advanced NSCLC is impeded by the low sensitivity of the tumor to cytostatic agents and the co-existence of many diseases, which substrate is, like lung cancer, cigarette smoking. Along with the development of molecular biology, targeted therapy has started to be used, affecting specific signaling pathways involved in the processes of oncogenesis...
May 17, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
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