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https://www.readbyqxmd.com/read/27801981/heterogeneity-of-the-resistance-to-gefitinib-treatment-in-a-non-small-cell-lung-cancer-patient-with-active-epidermal-growth-factor-receptor-mutation
#1
Chong-Rui Xu, Wen-Zhao Zhong, Qing Zhou, Xu-Chao Zhang, Jin-Ji Yang, Yi-Long Wu
We report the case of a 37-year-old male non-small cell lung cancer patient with an active epidermal growth factor receptor (EGFR) mutation who received gefitinib as first-line treatment. After 13.7 months, the patient experienced disease progression and was treated with platinum-based doublet chemotherapy plus gefitinib for 5.4 months. A subsequent lung biopsy showed cMET overexpression; therefore, the patient received a cMET inhibitor with the gefitinib. The response in the different lesions of several organs was diverse...
November 1, 2016: Thoracic Cancer
https://www.readbyqxmd.com/read/27676475/o-04-profiling-of-met-amplified-non-small-cell-lung-cancer-nsclc-correlation-to-cmet-protein-expression-met-exon-14-skipping
#2
David Arguello, Andreas Voss, Zoran Gatalica, Ryan Bender
No abstract text is available yet for this article.
October 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27573756/crizotinib-resistance-implications-for-therapeutic-strategies
#3
REVIEW
I Dagogo-Jack, A T Shaw
In 2007, a chromosomal rearrangement resulting in a gene fusion leading to expression of a constitutively active anaplastic lymphoma kinase (ALK) fusion protein was identified as an oncogenic driver in non-small-cell lung cancer (NSCLC). ALK rearrangements are detected in 3%-7% of patients with NSCLC and are particularly enriched in younger patients with adenocarcinoma and a never or light smoking history. Fortuitously, crizotinib, a small molecule tyrosine kinase inhibitor initially developed to target cMET, was able to be repurposed for ALK-rearranged (ALK+) NSCLC...
September 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27566252/genomic-alterations-in-neuroendocrine-cancers-of-the-ovary
#4
George Yaghmour, Philippe Prouet, Eric Wiedower, Omer Hassan Jamy, Rebecca Feldman, Jason C Chandler, Manjari Pandey, Mike G Martin
BACKGROUND: As we have previously reported, small cell carcinoma of the ovary (SCCO) is a rare, aggressive form of ovarian cancer associated with poor outcomes. In an effort to identify new treatment options, we utilized comprehensive genomic profiling to assess the potential for novel therapies in SCCO. METHODS: Patients with SCCO, SCCO-HT (hypercalcemic type), neuroendocrine tumors of the ovary (NET-O), and small cell carcinoma of the lung (SCLC) profiled by Caris Life Sciences between 2007-2015 were identified...
August 26, 2016: Journal of Ovarian Research
https://www.readbyqxmd.com/read/27546183/dual-transcript-and-protein-quantification-in-a-massive-single-cell-array
#5
Seung-Min Park, Jae Young Lee, Soongweon Hong, Sang Hun Lee, Ivan K Dimov, Hojae Lee, Susie Suh, Qiong Pan, Keyu Li, Anna M Wu, Shannon M Mumenthaler, Parag Mallick, Luke P Lee
Recently, single-cell molecular analysis has been leveraged to achieve unprecedented levels of biological investigation. However, a lack of simple, high-throughput single-cell methods has hindered in-depth population-wide studies with single-cell resolution. We report a microwell-based cytometric method for simultaneous measurements of gene and protein expression dynamics in thousands of single cells. We quantified the regulatory effects of transcriptional and translational inhibitors on cMET mRNA and cMET protein in cell populations...
October 7, 2016: Lab on a Chip
https://www.readbyqxmd.com/read/27362807/tc-n19-a-novel-dual-inhibitor-of-egfr-and-cmet-efficiently-overcomes-egfr-tki-resistance-in-non-small-cell-lung-cancer-cells
#6
D-W Wu, T-C Chen, H-S Huang, H Lee
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) show a clinical benefit when used to treat patients with EGFR-mutated non-small-cell lung cancer (NSCLC), but this treatment unfortunately fails in patients with TKI-resistant tumors. We here provide evidence that TC-N19 (N19), a novel dual inhibitor of EGFR and cMET, efficiently overcomes the EGFR-TKI resistance in EGFR-mutated NSCLC cells via simultaneous degradation of both proteins by ubiquitin proteasomes. Comparison with HSP90 inhibitor treatment and knockdown of EGFR and cMET by small hairpin RNAs reveal that the reduction of EGFR and cMET expression by N19 is responsible for overcoming the intrinsic TKI resistance mediated by paxillin (PXN) in high PXN-expressing cells, PXN-overexpressing PC9 cells (PC9-PXN), the EGFR-T790M-mediated TKI resistance in H1975 and CL97 cells, and the acquired resistance to gefitinib in gefitinib-resistant PC9 cells (PC9GR)...
June 30, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27329168/genomic-landscape-of-small-cell-carcinoma-of-the-breast-contrasted-to-small-cell-carcinoma-of-the-lung
#7
Brennan McCullar, Manjari Pandey, George Yaghmour, Felicia Hare, Kruti Patel, Matthew Stein, Rebecca Feldman, Jason C Chandler, Michael G Martin
Small cell carcinoma of the breast is a rare, aggressive form of breast cancer that is associated with extremely poor outcomes [1]. In an effort to identify possible targets for treatment, we utilized comprehensive genomic profiling in small cell carcinoma of the breast. Under an IRB approved protocol, we identified patients with small cell carcinoma of the breast and small cell carcinoma of the lung profiled by Caris Life Sciences between 2007 and 2015. Tumors were assessed with up to 25 immunohistochemical stains, in situ hybridization of cMET, EGFR, HER2, PIK3CA, and TOP2A, and next generation sequencing as well as Sanger sequencing of 47 genes...
July 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27223456/cmet-exon-14-skipping-from-the-structure-to-the-clinic
#8
REVIEW
Nele Van Der Steen, Elisa Giovannetti, Patrick Pauwels, Godefridus J Peters, David S Hong, Federico Cappuzzo, Fred R Hirsch, Christian Rolfo
The abnormal stimulation of the multiple signal transduction pathways downstream of the receptor tyrosine kinase mesenchymal-epithelial transition factor (cMET) promotes cellular transformation, tumor motility, and invasion. Therefore, cMET has been the focus of prognostic and therapeutic studies in different tumor types, including non-small cell lung cancer. In particular, several cMET inhibitors have been developed as innovative therapeutic candidates and are currently under investigation in clinical trials...
September 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27216193/a-novel-bispecific-antibody-targeting-egfr-and-cmet-is-effective-against-egfr-inhibitor-resistant-lung-tumors
#9
Sheri L Moores, Mark L Chiu, Barbara S Bushey, Kristen Chevalier, Leopoldo Luistro, Keri Dorn, Randall J Brezski, Peter Haytko, Thomas Kelly, Sheng-Jiun Wu, Pauline L Martin, Joost Neijssen, Paul W H I Parren, Janine Schuurman, Ricardo M Attar, Sylvie Laquerre, Matthew V Lorenzi, G Mark Anderson
Non-small cell lung cancers (NSCLC) with activating EGFR mutations become resistant to tyrosine kinase inhibitors (TKI), often through second-site mutations in EGFR (T790M) and/or activation of the cMet pathway. We engineered a bispecific EGFR-cMet antibody (JNJ-61186372) with multiple mechanisms of action to inhibit primary/secondary EGFR mutations and the cMet pathway. JNJ-61186372 blocked ligand-induced phosphorylation of EGFR and cMet and inhibited phospho-ERK and phospho-AKT more potently than the combination of single receptor-binding antibodies...
July 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27146445/pattern-and-prognostic-implications-of-cardiac-metastases-among-patients-with-advanced-systemic-cancer-assessed-with-cardiac-magnetic-resonance-imaging
#10
Shawn C Pun, Andrew Plodkowski, Matthew J Matasar, Yulia Lakhman, Darragh F Halpenny, Dipti Gupta, Chaya Moskowitz, Jiwon Kim, Richard Steingart, Jonathan W Weinsaft
BACKGROUND: Cardiac magnetic resonance (CMR) imaging is well validated for tissue characterization of cardiac masses but has not been applied to study pattern and prognostic implications of cardiac metastases (CMETs) among patients with systemic cancer. METHODS AND RESULTS: The population consisted of 60 patients with stage IV cancer (32 patients with CMETs, 28 diagnosis-matched controls) undergoing CMR. CMET was defined as a discrete mass with vascular tissue properties on delayed enhancement CMR...
May 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27096542/differential-response-to-ablative-ionizing-radiation-in-genetically-distinct-non-small-cell-lung-cancer-cells
#11
Ayman Oweida, Zeinab Sharifi, Hani Halabi, Yaoxian Xu, Siham Sabri, Bassam Abdulkarim
Stereotactic ablative radiotherapy (SABR) has emerged as a highly promising treatment for medically inoperable early-stage non-small cell lung cancer patients. Treatment outcomes after SABR have been excellent compared to conventional fractionated radiotherapy (CFRT). However, the biological determinants of the response to ablative doses of radiation remain poorly characterized. Furthermore, there's little data on the cellular and molecular response of genetically distinct NSCLC subtypes to radiation. We assessed the response of 3 genetically distinct lung adenocarcinoma cell lines to ablative and fractionated ionizing radiation (AIR and FIR)...
April 2, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27036872/hepatocyte-growth-factor-as-a-downstream-mediator-of-vascular-endothelial-growth-factor-dependent-preservation-of-growth-in-the-developing-lung
#12
Gregory Seedorf, Alexander J Metoxen, Robert Rock, Neil Markham, Sharon Ryan, Thiennu Vu, Steven H Abman
Impaired vascular endothelial growth factor (VEGF) signaling contributes to the pathogenesis of bronchopulmonary dysplasia (BPD). We hypothesized that the effects of VEGF on lung structure during development may be mediated through its downstream effects on both endothelial nitric oxide synthase (eNOS) and hepatocyte growth factor (HGF) activity, and that, in the absence of eNOS, trophic effects of VEGF would be mediated through HGF signaling. To test this hypothesis, we performed an integrative series of in vitro (fetal rat lung explants and isolated fetal alveolar and endothelial cells) and in vivo studies with normal rat pups and eNOS(-/-) mice...
June 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27028852/a-window-of-opportunity-study-of-potential-tumor-and-soluble-biomarkers-of-response-to-preoperative-erlotinib-in-early-stage-non-small-cell-lung-cancer
#13
Adrian G Sacher, Lisa W Le, Humberto Lara-Guerra, Thomas K Waddell, Shingo Sakashita, Zhuo Chen, Lucia Kim, Tong Zhang, Suzanne Kamel-Reid, Alexandra Salvarrey, Gail Darling, Kazuhiro Yasufuku, Shaf Keshavjee, Marc de Perrot, Frances A Shepherd, Geoffrey Liu, Ming Sound Tsao, Natasha B Leighl
BACKGROUND: Erlotinib is highly active in EGFR mutant NSCLC, but may benefit some with wild-type tumors. We examined pre-operative erlotinib in early stage NSCLC to assess response and correlation with potential biomarkers. RESULTS: Twenty-five patients were enrolled; 22 received erlotinib treatment and were evaluable (median follow-up 4.4 years). Histology was predominantly adenocarcinoma although 31% had squamous carcinoma. PET response was observed in 2 patients (9%), both with squamous carcinoma...
May 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/26854464/chromosome-7-deregulation-in-non-small-cell-lung-carcinoma-molecular-landscape
#14
Evangelos Tsiambas, Vasileios Ragos, Alicia Y Lefas, Stavros N Georgiannos, Dimitra Grapsa, Dimitra Grapsa, Efstratios Patsouris, Konstantinos Syrigos
Lung cancer exhibits an increasing incidence and a high mortality rate worldwide. Non-small cell lung carcinoma (NSCLC)constitutes the majority of patients with lung cancer (about 85% of all pathologically defined lung cancer cases). A broad spectrum of genomic imbalances, including chromosome polysomy/aneuploidy or specific gene deregulation mechanisms, such as point mutations, deletions and amplifications has been already identified in the corresponding patients, modifying their response rates to novel targeted therapeutic regimens, and affecting also their life span...
November 2015: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/26463323/-bufalin-reverses-hepatocyte-growth-factor-induced-resistance-to-afatinib-in-h1975-lung-cancer-cells
#15
Xiaohong Kang, Ping Lu, Yanhui Cui, Ying Wang, Qingqin Zhang, Yabin Gong, Zhenye Xu
OBJECTIVE: To investigate the effects of bufalin in reversing hepatocyte growth factor (HGF)-induced resistance to afatinib in H1975 lung cancer cells, and explore its possible mechanism. METHODS: The afatinib-resistant H1975 lung cancer cells (H1975AR) were induced by exogenous HGF and transfected with recombinant adenoviral vector Ad-HGF-GFP. The cytostatic effects of bufalin, afatinib and bufalin plus afatinib on H1975AR cells were evaluated by MTT assay. The impact of combined therapy with bufalin and afatinib on invasion of H1975AR cells was determined by transwell migration assay...
July 2015: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/26310485/yangzheng-xiaoji-exerts-anti-tumour-growth-effects-by-antagonising-the-effects-of-hgf-and-its-receptor-cmet-in-human-lung-cancer-cells
#16
Wen G Jiang, Lin Ye, Fiona Ruge, Sioned Owen, Tracey Martin, Ping-Hui Sun, Andrew J Sanders, Jane Lane, Lucy Satherley, Hoi P Weeks, Yong Gao, Cong Wei, Yiling Wu, Malcolm D Mason
BACKGROUND: Hepatocyte growth factor (HGF) is a cytokine that has a profound effect on cancer cells by stimulating migration and invasion and acting as an angiogenic factor. In lung cancer, the factor also plays a pivotal role and is linked to a poor outcome in patients. In particular, HGF is known to work in combination with EGF on lung cancer cells. In the present study, we investigated the effect of a traditional Chinese medicine reported in cancer therapies, namely YangZheng XiaoJi (YZXJ) on lung cancer and on HGF mediated migration and invasion of lung cancer cells...
2015: Journal of Translational Medicine
https://www.readbyqxmd.com/read/25815459/cmet-in-nsclc-can-we-cut-off-the-head-of-the-hydra-from-the-pathway-to-the-resistance
#17
REVIEW
Nele Van Der Steen, Patrick Pauwels, Ignacio Gil-Bazo, Eduardo Castañon, Luis Raez, Federico Cappuzzo, Christian Rolfo
In the last decade, the tyrosine kinase receptor cMET, together with its ligand hepatocyte growth factor (HGF), has become a target in non-small cell lung cancer (NSCLC). Signalization via cMET stimulates several oncological processes amongst which are cell motility, invasion and metastasis. It also confers resistance against several currently used targeted therapies, e.g., epidermal growth factor receptor (EGFR) inhibitors. In this review, we will discuss the basic structure of cMET and the most important signaling pathways...
2015: Cancers
https://www.readbyqxmd.com/read/25511614/the-role-of-cmet-in-non-small-cell-lung-cancer-resistant-to-egfr-inhibitors-did-we-really-find-the-target
#18
REVIEW
Francesco Passiglia, Nele Van Der Steen, Luis Raez, Patrick Pauwels, Ignacio Gil-Bazo, Edgardo Santos, Daniele Santini, Giovanni Tesoriere, Antonio Russo, Giuseppe Bronte, Karen Zwaenepoel, Federico Cappuzzo, Christian Rolfo
The advent of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represented the most important innovation in NSCLC treatment over the last years. However, despite a great initial activity, secondary mutations in the same target, or different alterations in other molecular pathways, inevitably occur, leading to the emergence of acquired resistance, in median within the first year of treatment. In this scenario, the mesenchymal-epidermal transition (cMET) tyrosine kinase receptor and its natural ligand, the hepatocyte growth factor (HGF), seem to play an important role...
2014: Current Drug Targets
https://www.readbyqxmd.com/read/25351743/cabozantinib-overcomes-crizotinib-resistance-in-ros1-fusion-positive-cancer
#19
Ryohei Katayama, Yuka Kobayashi, Luc Friboulet, Elizabeth L Lockerman, Sumie Koike, Alice T Shaw, Jeffrey A Engelman, Naoya Fujita
PURPOSE: ROS1 rearrangement leads to constitutive ROS1 activation with potent transforming activity. In an ongoing phase I trial, the ALK tyrosine kinase inhibitor (TKI) crizotinib shows remarkable initial responses in patients with non-small cell lung cancer (NSCLC) harboring ROS1 fusions; however, cancers eventually develop crizotinib resistance due to acquired mutations such as G2032R in ROS1. Thus, understanding the crizotinib-resistance mechanisms in ROS1-rearranged NSCLC and identification of therapeutic strategies to overcome the resistance are required...
January 1, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/25287912/predictive-molecular-markers-in-metastases-to-the-central-nervous-system-recent-advances-and-future-avenues
#20
REVIEW
Anna Sophie Berghoff, Rupert Bartsch, Adelheid Wöhrer, Berthold Streubel, Peter Birner, Johan M Kros, Priscilla K Brastianos, Andreas von Deimling, Matthias Preusser
Metastases to the central nervous system (CNS) are common in several cancer types. For most primary tumors that commonly metastasize to the CNS, molecular biomarker analyses are recommended in the clinical setting for selection of appropriate targeted therapies. Therapeutic efficacy of some of these agents has been documented in patients with brain metastases, and molecular testing of CNS metastases should be considered in the clinical setting. Here, we summarize the clinically relevant biomarker tests that should be considered in neurosurgical specimens based on the current recommendations of the European Society of Medical Oncology (ESMO) or the National Comprehensive Cancer Network (NCCN) for the most relevant primary tumor types: lung cancer (EGFR mutations, ALK rearrangement, BRAF mutations), breast cancer (HER2 amplification, steroid receptor overexpression), melanoma (BRAF mutations), and colorectal cancer (RAS mutations)...
December 2014: Acta Neuropathologica
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