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Egfr-tki treatment for lung cancer

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https://www.readbyqxmd.com/read/28927112/non-small-cell-lung-cancer-pc-9-cells-exhibit-increased-sensitivity-to-gemcitabine-and-vinorelbine-upon-acquiring-resistance-to-egfr-tyrosine-kinase-inhibitors
#1
Junko Hamamoto, Hiroyuki Yasuda, Kaito Aizawa, Makoto Nishino, Shigenari Nukaga, Toshiyuki Hirano, Ichiro Kawada, Katsuhiko Naoki, Tomoko Betsuyaku, Kenzo Soejima
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) are widely used for the treatment of non-small cell lung cancers (NSCLCs) harboring EGFR-activating mutations. However, lung cancer cells inevitably acquire resistance to these EGFR-TKIs. The majority of patients whose lung cancer acquires resistance to EGFR-TKIs are subjected to treatment using cytotoxic agents. The present study aimed to determine if lung cancer cells acquiring resistance to EGFR-TKIs also develop altered sensitivity to cytotoxic agents...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28915640/marsdenia-tenacissima-extract-overcomes-axl-and-met-mediated-erlotinib-and-gefitinib-cross-resistance-in-non-small-cell-lung-cancer-cells
#2
Shu-Yan Han, Wei Zhao, Hai-Bo Han, Hong Sun, Dong Xue, Yan-Na Jiao, Xi-Ran He, Shan-Tong Jiang, Ping-Ping Li
Tyrosine kinase inhibitors (TKIs) are an effective treatment strategy for non-small cell lung cancer (NSCLC) patients harboring mutations that result in constitutive activation of the epidermal growth factor receptor (EGFR). However, most patients eventually develop resistance to TKIs. This occurs due to additional EGFR mutations or the activation of bypass signaling pathways. In our previous work, we demonstrated that Marsdenia tenacissima extract (MTE) restored gefitinib sensitivity in resistant NSCLC cells with EGFR T790M or K-ras mutations...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912406/-a-retrospective-study-analyzing-the-clinical-course-of-patients-with-non-small-cell-lung-cancer-receiving-local-or-systemic-therapy-after-post-operative-recurrence
#3
Minehiko Inomata, Hiroaki Tanaka, Kazuki Shimokawa, Kotaro Tokui, Seisuke Okazawa, Chihiro Taka, Kenta Kambara, Shingo Imanishi, Toru Yamada, Toshiro Miwa, Ryuji Hayashi, Shoko Matsui, Tatsuhiko Kashii, Takahiro Homma, Kuninori Nomura, Yoshinori Doki, Kazuyuki Tobe
BACKGROUND: While systemic therapy is one of the therapeutic options available for post-operative recurrence of non-small cell lung cancer, efficacy of local therapy for locoregional recurrence or limited metastatic lesions has also been reported. OBJECTIVE: We aimed to evaluate the clinical course of patients with post-operative recurrence(locoregional or limited metastatic lesion)after receiving local or systemic therapy. METHODS: Clinical data were retrospectively analyzed and survival duration was compared using the logrank test...
September 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28911086/large-scale-prospective-screening-of-egfr-mutations-in-the-blood-of-advanced-nsclc-patients-to-guide-treatment-decisions
#4
C Mayo-de-Las-Casas, N Jordana-Ariza, M Garzón-Ibañez, A Balada-Bel, J Bertrán-Alamillo, S Viteri-Ramírez, N Reguart, M A Muñoz-Quintana, P Lianes-Barragan, C Camps, E Jantús, J Remon-Massip, S Calabuig, D Aguiar, M L Gil, N Viñolas, A K Santos-Rodríguez, M Majem, B García-Peláez, S Villatoro, A Pérez-Rosado, J C Monasterio, E Ovalle, M J Catalán, R Campos, D Morales-Espinosa, A Martínez-Bueno, M González-Cao, X González, I Moya-Horno, A E Sosa, N Karachaliou, R Rosell, M A Molina-Vila
Background: In a significant percentage of advanced non-small-cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses. We prospectively analyzed if circulating-free DNA (cfDNA) purified from blood can be used as a surrogate in this setting to select patients for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Patients and methods: Blood samples were collected in 119 hospitals from 1138 advanced NSCLC patients at presentation (n = 1033) or at progression to EGFR-TKIs (n = 105) with no biopsy or insufficient tumor tissue...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28894381/continuous-egfr-tyrosine-kinase-inhibitor-treatment-with-or-without-chemotherapy-beyond-gradual-progression-in-non-small-cell-lung-cancer-patients
#5
Ling Peng, Yina Wang, Yemin Tang, Lei Zeng, Junfang Liu, Zhu Zeng, Jian Liu, Peng Shi, Xianghua Ye, Qiong Zhao
BACKGROUND: Several clinical studies have demonstrated that continuous administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) could provide additional survival benefit for advanced non-small cell lung cancer (NSCLC) patients who had benefited from prior EGFR TKI therapy. However, whether EGFR TKI combined with chemotherapy could further prolong survival in patients with gradual progression is still unclear. The present study was conducted to evaluate the clinical outcome of continuous EGFR TKI treatment in combination with chemotherapy (combination group) versus continuous EGFR TKI treatment only (monotherapy group) in such a clinical setting...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28887613/theoretical-method-for-evaluation-of-therapeutic-effects-and-adverse-effects-of-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-in-clinical-treatment
#6
Koji Kimura, Risa Takayanagi, Tomoki Fukushima, Yasuhiko Yamada
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used for non-small cell lung cancer patients with an EGFR gene mutation. However, skin disorders are known as adverse events. In the present study, we investigated whether EGFR-TK occupancy is useful as an index for assessing clinical efficacy and adverse events for the proper use and development of EGFR-TKIs. Average binding occupancies (Φ ss) of EGFR-TKIs, gefitinib and erlotinib, for the EGFR-TK of cancer or skin cells were calculated...
September 8, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28881815/clinicopathological-characteristics-of-ros1-and-ret-rearranged-nsclc-in-caucasian-patients-data-from-a-cohort-of-713-non-squamous-nsclc-lacking-kras-egfr-her2-braf-pik3ca-alk-alterations
#7
Frédéric Dugay, Francisco Llamas-Gutierrez, Marjory Gournay, Sarah Medane, François Mazet, Dan Christian Chiforeanu, Emmanuelle Becker, Régine Lamy, Hervé Léna, Nathalie Rioux-Leclercq, Marc-Antoine Belaud-Rotureau, Florian Cabillic
Targeted therapies have substantially changed the management of non-small cell lung cancer (NSCLC) patients with driver oncogenes. Given the high frequency, EGFR and ALK aberrations were the first to be detected and paved the way for tyrosine kinase inhibitor (TKI) treatments. Other kinases such as ROS1 and more recently RET have emerged as promising targets, and ROS1 and RET TKIs are already available for precision medicine. We screened a large cohort of 713 Caucasian non-squamous NSCLC patients lacking EGFR/KRAS/BRAF/HER2/PI3KCA/ALK aberrations for ROS1 and RET rearrangements using fluorescence in situ hybridization to determine the frequency and clinicopathological characteristics of ROS1- and RET-positive patients...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28880737/cost-effectiveness-of-osimertinib-in-the-uk-for-advanced-egfr-t790m-non-small-cell-lung-cancer
#8
Evelina Bertranou, Carolyn Bodnar, Viktor Dansk, Alastair Greystoke, Samuel Large, Matthew Dyer
AIM: This study presents the cost-utility analysis that was developed to inform the NICE health technology assessment of osimertinib versus platinum-based doublet chemotherapy (PDC) in patients with EGFR-T790M mutation-positive non-small cell lung cancer (NSCLC) who have progressed on epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. METHODS AND MATERIALS: A partitioned survival model with three health states (progression-free, progressed disease, and death) from a UK payer perspective and over lifetime (15 years) was developed...
September 7, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28880013/osimertinib-azd9291-decreases-programmed-death-ligand-1-in-egfr-mutated-non-small-cell-lung-cancer-cells
#9
Xiao-Ming Jiang, Yu-Lian Xu, Mu-Yang Huang, Le-Le Zhang, Min-Xia Su, Xiuping Chen, Jin-Jian Lu
Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). In NSCLC patients, an EGFR mutation is likely to be correlated with high levels of expression of programmed death ligand-1 (PD-L1). Here, we showed that osimertinib decreased PD-L1 expression in human EGFR mutant NSCLC cells in vitro. Osimertinib (125 nmol/L) markedly suppressed PD-L1 mRNA expression in both NCI-H1975 and HCC827 cells...
September 7, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28879074/a-case-report-of-egfr-mutant-lung-adenocarcinoma-that-acquired-resistance-to-egfr-tyrosine-kinase-inhibitors-with-t790m-mutation-and-epithelial-to-mesenchymal-transition
#10
Nana Zhang, Depu Wang, Xiaofeng Li, Zhe Yang, Guanjun Zhang, Yili Wang, Chunbao Wang
Although a secondary mutation and the epithelial-to-mesenchymal transition (EMT) are encountered very often in patients received the EGFR-TKI targeted treatment. The entire detrimental morphological change of the cancer entity was rare reported. Herein we report a case that acquired resistance to EGFR-TKI with T790M mutation and complete EMT morphological change of the tumor tissue. The primary lung tumor from a 52-year-old woman was diagnosed with moderate differentiated adenocarcinoma, with intensively positiveTTF-1 and E-cadherin in differentiated glandular structure but not the budding cancer cell cluster which with an intensive Vimentin staining...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28870456/pharmacological-synergism-of-2-2-dichloroacetophenone-and-egfr-tki-to-overcome-tki-induced-resistance-in-nsclc-cells
#11
Zheng Yang, Xiaohui Hu, Shaolin Zhang, Wen Zhang, Kin Yip Tam
Combination treatment has been used as one of the therapeutic approaches for patients suffering from lung cancer, either to cope with the issue of acquired drug resistance due to prolong the use of a particular EGFR-TKi treatment, or to decrease the doses of each compound in order to reduce potential toxicity. 2,2-dichloroacetophenone (DAP) was reported as a PDK inhibitor recently, which is much more potent than dichloroacetate (DCA) in anti-cancer therapy. In this study, we applied DAP in combined with EGFR-TKis, erlotinib or gefitinib in NSCLC cell lines and NSCLC xenograft model...
September 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28868565/comparison-of-the-amplification-refractory-mutation-system-super-amplification-refractory-mutation-system-and-droplet-digital-pcr-for-t790%C3%A2-m-mutation-detection-in-non-small-cell-lung-cancer-after-failure-of-tyrosine-kinase-inhibitor-treatment
#12
Lucheng Zhu, Shirong Zhang, Yanping Xun, Yanping Jiang, Bing Xia, Xueqin Chen, Limin Wang, Hong Jiang, Shenglin Ma
Plasma mutation detection has the advantages of non-invasiveness and accessibility. Here, we evaluated three methods, the amplification refractory mutation system (ARMS), second-generation ARMS (SuperARMS), and droplet digital PCR (ddPCR), to assess their concordance and feasibility for the detection of mutations in plasma samples. Non-small lung cancer patients with stage IIIB/IV that were resistant to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment were enrolled. Blood samples were collected within 14 days after TKI resistance...
September 3, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28866043/clinical-factors-predicting-detection-of-t790m-mutation-in-rebiopsy-for-egfr-mutant-non-small-cell-lung-cancer
#13
Takahisa Kawamura, Hirotsugu Kenmotsu, Shota Omori, Kazuhisa Nakashima, Kazushige Wakuda, Akira Ono, Tateaki Naito, Haruyasu Murakami, Katsuhiro Omae, Keita Mori, Yusuke Tanigawara, Takashi Nakajima, Yasuhisa Ohde, Masahiro Endo, Toshiaki Takahashi
BACKGROUND: T790M, a secondary epidermal growth factor receptor (EGFR) mutation, accounts for approximately 50% of acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs). To facilitate the use of third-generation EGFR-TKIs to potentially overcome T790M-mediated resistance, we evaluated the clinical factors influencing the incidence of T790M mutation. PATIENTS AND METHODS: We retrospectively screened patients with non-small-cell lung cancer harboring EGFR mutations with progressive disease who were rebiopsied between January 2013 and December 2016...
August 10, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28864950/correlation-of-early-pet-findings-with-tumor-response-to-molecular-targeted-agents-in-patients-with-advanced-driver-mutated-non-small-cell-lung-cancer
#14
Tomonobu Koizumi, Toshirou Fukushima, Daisuke Gomi, Takashi Kobayashi, Nodoka Sekiguchi, Keiko Mamiya, Kazunari Tateishi, Akane Katou, Kazuhiro Oguchi
Recent advances in positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) have facilitated not only the diagnosis and staging of lung cancer, but also the prediction of treatment outcome. The present study was designed to assess the usefulness of early FDG-PET examination for predicting subsequent tumor size reduction in response to molecular targeted agents in metastatic non-small cell lung cancer (NSCLC) with sensitive gene anomalies. I. In 29 targeted lesions of 10 NSCLC patients, changes in FDG uptake before and on day 7 after the initiation of molecular targeted therapy (gefitinib, n = 7; crizotinib, n = 3) were compared with subsequent radiographic tumor size reduction by RECIST...
September 1, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28860885/osimertinib-in-the-treatment-of-non-small-cell-lung-cancer-design-development-and-place-in-therapy
#15
REVIEW
Mariacarmela Santarpia, Alessia Liguori, Niki Karachaliou, Maria Gonzalez-Cao, Maria Grazia Daffinà, Alessandro D'Aveni, Grazia Marabello, Giuseppe Altavilla, Rafael Rosell
The discovery of epidermal growth factor receptor (EGFR) mutations and subsequent demonstration of the efficacy of genotype-directed therapies with EGFR tyrosine kinase inhibitors (TKIs) marked the advent of the era of precision medicine for non-small-cell lung cancer (NSCLC). First- and second-generation EGFR TKIs, including erlotinib, gefitinib and afatinib, have consistently shown superior efficacy and better toxicity compared with first-line platinum-based chemotherapy and currently represent the standard of care for EGFR-mutated advanced NSCLC patients...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28855035/-retrospective-study-of-efficacy-in-bim-gene-polymorphism-on-first-line-egfr-tkis-treatment-for-advanced-lung-adenocarcinoma
#16
Kun Qian, Yi Zhang, Xiuyi Zhi
BACKGROUND: The aim of this study is to detect the BIM polymorphism in 85 formalin-fixed and parrffin-embedded (FFPE) and some blood samples of advanced lung adenocarcinoma patients and study the relativity betweenthe BIM polymorphism and tyrosine kinase inhibitor (TKI). The correlation between BIM detection of different types of specimens was discussed. METHODS: There were 85 patients who were diagnosed as advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) 19 or 21 exon mutation in thoracic surgery of Xuanwu Hospital from February 2013 to November 2014, all of who were received EGFR-TKI as first-line treatment in the study...
August 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28854272/overall-survival-in-egfr-mutated-non-small-cell-lung-cancer-patients-treated-with-afatinib-after-egfr-tki-and-resistant-mechanisms-upon-disease-progression
#17
A J van der Wekken, J L Kuiper, A Saber, M M Terpstra, J Wei, T J N Hiltermann, E Thunnissen, D A M Heideman, W Timens, E Schuuring, K Kok, E F Smit, A van den Berg, H J M Groen
PURPOSE: To determine survival in afatinib-treated patients after treatment with first-generation EGFR tyrosine kinase inhibitors (TKIs) and to study resistance mechanisms in afatinib-resistant tumors. METHODS: Characteristics and survival of patients treated with afatinib after resistance to erlotinib or gefitinib in two large Dutch centers were collected. Whole exome sequencing (WES) and pathway analysis was performed on available pre- and post-afatinib tumor biopsies and normal tissue...
2017: PloS One
https://www.readbyqxmd.com/read/28840704/-meta-analysis-on-effectiveness-and-safety-of-traditional-chinese-medicine-combined-with-first-generation-egfr-tki-in-treating-advanced-non-small-cell-lung-cancer
#18
Wei He, Miao Cheng
To evaluate the efficacy and safety of traditional Chinese medicine combined with first-generation EGFR-TKI in treating advanced non-small cell lung cancer (NSCLC). China biomedical literature database (CBM), China Journal Full-text Database (CNKI), VIP, PubMed, CochraneLibrary, EMbase and other Chinese and English databases were searched for randomized and clinical controlled trials of traditional Chinese medicine combined with first-generation EGFR-TKI in treating advanced NSCLC. The statistical effect was measured by Revman 5...
July 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28839997/the-efficacy-and-toxicity-of-afatinib-in-advanced-egfr-positive-non-small-cell-lung-cancer-patients-after-failure-of-first-generation-tyrosine-kinase-inhibitors-a-systematic-review-and-meta-analysis
#19
Yaxiong Zhang, Siyu Miao, Fang Wang, Wenfeng Fang, Gang Chen, Xi Chen, Fang Yan, Xiaodan Huang, Manli Wu, Yan Huang, Li Zhang
BACKGROUND: The first generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, have become the standard first-line treatment for non-small-cell lung cancer (NSCLC) patients with EGFR mutation. However, there was no pooled analysis focused on the usage of the second-generation TKI, afatinib, in advanced EGFR-positive NSCLC patients after failure of first generation TKIs. Therefore, a meta-analysis was conducted to solve the above question...
July 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28839001/t790m-selective-egfr-tki-combined-with-dasatinib-as-an-optimal-strategy-for-overcoming-egfr-tki-resistance-in-t790m-positive-non-small-cell-lung-cancer
#20
Satomi Watanabe, Takeshi Yoshida, Hisato Kawakami, Naoki Takegawa, Junko Tanizaki, Hidetoshi Hayashi, Masayuki Takeda, Kimio Yonesaka, Junji Tsurutani, Kazuhiko Nakagawa
T790M mutation-selective epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated clinical benefits in non-small cell lung cancer (NSCLC) patients harboring T790M mutation, which is the major cause of resistance to EGFR-TKI. However, their efficacy is limited, possibly due to the emergence of apoptosis resistance in T790M-positive NSCLC. We previously identified Src family kinases as co-oncogenic drivers along with T790M and found that the Src inhibitor dasatinib combined with an irreversible or a preclinical T790M-selective EGFR-TKI enhanced anti-tumor activity in T790M-positive cells...
August 24, 2017: Molecular Cancer Therapeutics
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