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TKIs in ALK+ NSCLC

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https://www.readbyqxmd.com/read/29764505/xenograft-tumors-derived-from-malignant-pleural-effusion-of-the-patients-with-non-small-cell-lung-cancer-as-models-to-explore-drug-resistance
#1
Yunhua Xu, Feifei Zhang, Xiaoqing Pan, Guan Wang, Lei Zhu, Jie Zhang, Danyi Wen, Shun Lu
BACKGROUND: Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions show dramatic responses to specific tyrosine kinase inhibitors (TKIs); however, after 10-12 months, secondary mutations arise that confer resistance. We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK- and EGFR-targeted TKIs crizotinib and osimertinib, respectively...
May 9, 2018: Cancer communications
https://www.readbyqxmd.com/read/29737033/clonally-related-primary-alk-rearranged-adenocarcinoma-and-associated-metastatic-lesions
#2
You-Cai Zhu, Yun-Te Deng, Wen-Xian Wang, Chun-Wei Xu, Wu Zhuang, Kai-Qi Du
ALK rearrangement is a driver gene in non-small cell lung cancer (NSCLC). ALK-positive tumors are sensitive to ALK-tyrosine kinase inhibitors (TKIs). The detection of key driver genes is crucial to enable personalized treatment. Different histomorphological patterns have different driver genes. Herein, we report the case of a 42-year-old male patient diagnosed with adenocarcinoma with different histomorphologies in the primary lung site (mucinous type) and lymph node metastasis (solid type), of the same genotype, both presenting with ALK rearrangement but negative for EGFR mutation...
May 8, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29736685/emerging-trends-in-the-management-of-brain-metastases-from-non-small-cell-lung-cancer
#3
REVIEW
Thomas M Churilla, Stephanie E Weiss
PURPOSE OF REVIEW: To summarize current approaches in the management of brain metastases from non-small cell lung cancer (NSCLC). RECENT FINDINGS: Local treatment has evolved from whole-brain radiotherapy (WBRT) to increasing use of stereotactic radiosurgery (SRS) alone for patients with limited (1-4) brain metastases. Trials have established post-operative SRS as an alternative to adjuvant WBRT following resection of brain metastases. Second-generation TKIs for ALK rearranged NSCLC have demonstrated improved CNS penetration and activity...
May 7, 2018: Current Oncology Reports
https://www.readbyqxmd.com/read/29726292/treating-brain-metastases-in-non-small-cell-lung-cancer-patients-what-have-we-learnt-from-pharmaceutical-recent-clinical-trials
#4
Bin-Chi Liao, Chia-Chi Lin, James Chih-Hsin Yang
Brain metastases (BMs) develop in up to 40% of patients with non-small cell lung cancer (NSCLC). In many recent practice-changing clinical trials, patients with BM were included; however, only few trials reported intracranial efficacies in either post hoc or pre-planned analysis. Clinically meaningful intracranial efficacy data of novel agents have not been completely disclosed. Areas covered: The authors performed a systemic review of recent pharmaceutical clinical trials, mainly pivotal or practice-changing trials...
May 4, 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29707333/current-outcomes-of-postrecurrence-survival-in-patients-after-resection-of-non-small-cell-lung-cancer
#5
Tetsuya Mizuno, Takaaki Arimura, Hiroaki Kuroda, Noriaki Sakakura, Yasushi Yatabe, Yukinori Sakao
Background: Despite complete resection, patients with resectable non-small cell lung cancer (NSCLC) sometimes experience recurrence in various sites, generally with an unfavorable prognosis. Receptor tyrosine kinase inhibitors (TKIs) have produced a dramatic response in patients with advanced NSCLC harboring sensitive mutations. Methods: We retrospectively investigated 281 patients with recurrence who underwent complete resection of their NSCLC between January 2005 and December 2013 with tumors in which the status of epidermal growth factor receptor (EGFR) mutation, KRAS mutation, and anaplastic lymphoma kinase (ALK) rearrangement was confirmed...
March 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29666949/precision-medicine-against-alk-positive-non-small-cell-lung-cancer-beyond-crizotinib
#6
REVIEW
Biagio Ricciuti, Andrea De Giglio, Carmen Mecca, Cataldo Arcuri, Sabrina Marini, Giulio Metro, Sara Baglivo, Angelo Sidoni, Guido Bellezza, Lucio Crinò, Rita Chiari
Anaplastic lymphoma kinase (ALK) rearrangements represent the molecular driver of a subset of non-small cell lung cancers (NSCLCs). Despite the initial response, virtually all ALK-positive patients develop an acquired resistance to the ALK inhibitor crizotinib, usually within 12 months. Several next-generation ALK inhibitors have been developed in order to overcome crizotinib limitation, providing an unprecedented survival for this subset of patients. The aim of this review to summarize the current knowledge on ALK tyrosine kinase inhibitors (TKIs) in the treatment of advanced ALK-positive NSCLC, focusing on the role of novel ALK inhibitors in this setting...
April 17, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29662531/cystic-brain-metastases-in-alk-rearranged-non-small-cell-lung-cancer
#7
REVIEW
Guilherme Nader Marta, Renata Rodrigues da Cunha Colombo Bonadio, Renata Eiras Martins, Henrique Bortot Zuppani, Gilberto de Castro
The central nervous system (CNS) is a common site of disease progression in patients with non-small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK)-rearrangement treated with crizotinib. Cystic brain metastases (CBM) have been recently identified as one possible variant of this disease. An illustrative case report is presented along with a literature review performed in order to track relevant papers about CBM in ALK-rearranged NSCLC, including possible pathophysiology, differential diagnosis and treatment options for this condition...
2018: Ecancermedicalscience
https://www.readbyqxmd.com/read/29587818/5-3-imbalance-strategy-to-detect-alk-fusion-genes-in-circulating-tumor-rna-from-patients-with-non-small-cell-lung-cancer
#8
Yongqing Tong, Zhijun Zhao, Bei Liu, Anyu Bao, Hongyun Zheng, Jian Gu, Mary McGrath, Ying Xia, Bihua Tan, Chunhua Song, Yan Li
BACKGROUND: Detecting an ALK fusion gene in patients with non-small cell lung cancer (NSCLC) could provide evidence to guide individualized therapy. METHODS: The 5'/3' imbalance strategy for quantitative reverse transcription-PCR (RT-qPCR) was developed to detect ALK fusion genes in circulating tumor RNA (ctRNA) of NSCLC patients. RESULTS: This method was validated in patients with the ALK fusion gene confirmed by next generation sequencing (NGS)...
March 27, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29572000/pd-l1-expression-in-lung-adenocarcinoma-harboring-egfr-mutations-or-alk-rearrangements
#9
Yasuto Yoneshima, Kayo Ijichi, Satoshi Anai, Keiichi Ota, Kohei Otsubo, Eiji Iwama, Kentaro Tanaka, Yoshinao Oda, Yoichi Nakanishi, Isamu Okamoto
OBJECTIVES: Expression of programmed cell death-ligand 1 (PD-L1) has been associated with clinical outcome of programmed cell death-1 (PD-1) pathway blockade in non-small cell lung cancer (NSCLC). The PD-L1 IHC 22C3 pharmDx assay, the only companion diagnostic for pembrolizumab therapy, has revealed that ∼30% of all NSCLCs express PD-L1 at a high level. The frequency of high PD-L1 expression in NSCLCs with known driver oncogenes has remained unclear, however. MATERIALS AND METHODS: We retrospectively evaluated PD-L1 expression with the 22C3 assay in tumor tissue of 80 lung adenocarcinoma patients including 71 with EGFR mutations and 9 with ALK rearrangements, all of whom were treated with corresponding tyrosine kinase inhibitors (TKIs)...
April 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29507704/incidence-and-risk-of-hepatic-toxicities-associated-with-anaplastic-lymphoma-kinase-inhibitors-in-the-treatment-of-non-small-cell-lung-cancer-a-systematic-review-and-meta-analysis
#10
Bing Liu, Maoxi Yuan, Yi Sun, Ziming Cheng, Zaiyong Zhang, Shizheng Hou, Xiangdong Wang, Jingfeng Liu
Background: Two anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (-TKIs) have been approved for the treatment of patients with ALK-rearranged (ALK-positive) advanced non-small cell lung cancer (NSCLC). Severe hepatotoxicity has been observed in several clinical studies. We aim to assess the incidence and risk of liver toxicity with these drugs by a systematic review and meta-analysis of clinical trials. Materials and Methods: The databases of PubMed, Web of Science and abstracts presented at oncology conferences' proceedings were searched for relevant studies from January 2000 to January 2017...
February 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29437006/enteral-administration-of-tkis-report-of-a-response-to-ceritinib-in-an-alk-positive-nsclc-patient-and-literature-review
#11
Francesco Facchinetti, Paola Bordi, Paola Bini, Livia Bidin, Roberta Camisa, Marcello Tiseo
INTRODUCTION: Several reports attest the feasibility and the favorable outcomes of kinase inhibitors administration through feeding tubes or percutaneous endoscopic gastrostomies (PEG), mainly in non-small cell lung cancer (NSCLC) patients exposed to first-generation compounds. Here we present the case of an ALK-positive NSCLC patient who achieved cerebral and extra-cranial disease response with ceritinib (a novel ALK inhibitor) administered through a nasogastric tube (NGT). We moreover provide a review gathering clinical successes obtained with targeted agents intake through NGT or PEG...
February 12, 2018: Current Drug Targets
https://www.readbyqxmd.com/read/29416799/correlation-among-genetic-variations-of-c-met-in-chinese-patients-with-non-small-cell-lung-cancer
#12
Jianchun Duan, Xiaodan Yang, Jun Zhao, Minglei Zhuo, Zhijie Wang, Tongtong An, Hua Bai, Jie Wang
Background: The purpose of our research was to determine the correlation of amplification, protein expression and somatic mutation of c-MET in IIIb-IV stage NSCLC (Non-small cell lung cancer). We also explored correlation of c-MET variation with clinical outcome. Results: c-MET expression was observed in 28.6% (56/196) cases, and among those 13.8% (27/196) were shown to be FISH positive. Only 2.67% patients in this study carried the c-MET mutation. Cases with c-MET FISH positive were all IHC positive ,but in IHC positive cases, only half were FISH positive...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29373100/impact-of-eml4-alk-variant-on-resistance-mechanisms-and-clinical-outcomes-in-alk-positive-lung-cancer
#13
Jessica J Lin, Viola W Zhu, Satoshi Yoda, Beow Y Yeap, Alexa B Schrock, Ibiayi Dagogo-Jack, Nicholas A Jessop, Ginger Y Jiang, Long P Le, Kyle Gowen, Philip J Stephens, Jeffrey S Ross, Siraj M Ali, Vincent A Miller, Melissa L Johnson, Christine M Lovly, Aaron N Hata, Justin F Gainor, Anthony J Iafrate, Alice T Shaw, Sai-Hong Ignatius Ou
Purpose Advanced anaplastic lymphoma kinase ( ALK) fusion-positive non-small-cell lung cancers (NSCLCs) are effectively treated with ALK tyrosine kinase inhibitors (TKIs). However, clinical outcomes in these patients vary, and the benefit of TKIs is limited as a result of acquired resistance. Emerging data suggest that the ALK fusion variant may affect clinical outcome, but the molecular basis for this association is unknown. Patients and Methods We identified 129 patients with ALK-positive NSCLC with known ALK variants...
April 20, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29336091/drug-resistance-in-anaplastic-lymphoma-kinase-rearranged-lung-cancer
#14
REVIEW
Ryohei Katayama
The anaplastic lymphoma kinase (ALK) gene encodes a receptor tyrosine kinase, and many kinds of ALK fusion genes have been found in a variety of carcinomas. There is almost no detectable expression of ALK in adults. However, through ALK gene rearrangement, the resultant ALK fusion protein is aberrantly overexpressed and dimerized through the oligomerization domains, such as the coiled-coil domain, in the fusion partner that induces abnormal constitutive activation of ALK tyrosine kinase. This results in dysregulated cell proliferation...
March 2018: Cancer Science
https://www.readbyqxmd.com/read/29331646/progress-in-the-management-of-advanced-thoracic-malignancies-in-2017
#15
REVIEW
Roberto Ferrara, Laura Mezquita, Benjamin Besse
The treatment paradigm of NSCLC underwent a major revolution during the course of 2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in response and overall survival both in unselected pretreated patients and in untreated patients with programmed death ligand 1 expression of 50% or more. Furthermore, compelling preliminary results were reported for new combinations of anti-programmed cell death 1/programmed death ligand 1 agents with chemotherapy or anti-cytotoxic T-lymphocyte associated protein 4 inhibitors...
March 2018: Journal of Thoracic Oncology
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
#16
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/29275314/radiotherapy-and-tyrosine-kinase-inhibitors-in-stage-iv-non-small-cell-lung-cancer-real-life-experience
#17
Paolo Borghetti, Marco Lorenzo Bonù, Elisa Roca, Sara Pedretti, Emiliano Salah, Anna Baiguini, Diana Greco, Luca Triggiani, Marta Maddalo, Niccolò Giaj Levra, Filippo Alongi, Stefano Maria Magrini, Michela Buglione
AIM: To investigate the role of conventional radiotherapy (RT) and stereotactic body radiotherapy (SBRT) in patients with epidermal growth factor (EGFR)-mutant or anaplastic lymphoma kinase (ALK) rearrangement-positive metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty patients with EGFR-mutated or ALK rearrangement-positive NSCLC were treated at our Institution. Radiotherapy was delivered before, after or concomitantly with tyrosine kinase inhibitors (TKIs)...
January 2018: In Vivo
https://www.readbyqxmd.com/read/29234489/molecular-insights-suppression-of-egfr-and-akt-activation-by-a-small-molecule-in-non-small-cell-lung-cancer
#18
Balaji Chandrasekaran, Ashish Tyagi, Arun K Sharma, Lu Cai, Murali Ankem, Chendil Damodaran
Epidermal growth factor receptor (EGFR) activation events and the mammalian target of rampamycin (mTOR) are considered important therapeutic targets in alleviating cancer conditions. The current treatment paradigm has shifted to personalized treatment strategies with tyrosine kinase inhibitors (TKIs) or anaplastic lymphoma kinase (ALK) inhibitors, due to low survival rates in non-small cell lung cancer (NSCLC) in terms of the prevailing platinum-based therapy. In the present study, we examined the anticancer potential of Verrucarin J (VJ), a small molecule, in NSCLC cell lines (H460 and A549)...
September 2017: Genes & Cancer
https://www.readbyqxmd.com/read/29174221/lung-toxicity-in-non-small-cell-lung-cancer-patients-exposed-to-alk-inhibitors-report-of-a-peculiar-case-and-systematic-review-of-the-literature
#19
REVIEW
Benedetta Pellegrino, Francesco Facchinetti, Paola Bordi, Mario Silva, Letizia Gnetti, Marcello Tiseo
Lung toxicity is a potential fatal effect involving non-small-cell lung cancer (NSCLC) patients exposed to tyrosine kinase inhibitors (TKIs). Moving from our experience regarding a patient who developed lung toxicity while receiving 2 different anaplastic lymphoma kinase (ALK)-TKIs, we performed a systematic review to assess the epidemiologic magnitude and the clinical significance of such toxicity in NSCLC patients treated with ALK-TKIs. Studies were identified using MEDLINE and additional sources (European Society for Medical Oncology, American Society of Clinical Oncology, and World Conference on Lung Cancer abstracts) in agreement with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane guidelines...
March 2018: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29167003/-prognostic-analysis-of-patients-with-advanced-non-small-cell-lung-cancer-%C3%A2-in-different-genotypes
#20
Ping Liu, Yuhua Wu, Lijuan Zhou, Na Qin, Quan Zhang, Hui Zhang, Xi Li, Xinyong Zhang, Jialin Lv, Xinjie Yang, Jinghui Wang, Shucai Zhang
BACKGROUND: Non-small cell lung cancer (NSCLC) has been transformed from the treatment according to histological type to genotype treatment model. The epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) genes are the most important drivers in lung cancer. The aim of this study is to explore the clinical characteristics and prognostic factors of patients with advanced NSCLC with different genotypes. METHODS: We retrospectively reviewed the clinical data of 553 advanced NSCLC patients with EGFR mutations and ALK positive who were hospitalized in the Beijing Chest Hospital from July 2004 to December 2015, and the independent prognostic factors of patients were analyzed by Cox proportional hazards regression model...
November 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
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