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https://www.readbyqxmd.com/read/28749535/inhibition-of-histone-deacetylases-sensitizes-egfr-tki-resistant-non-small-cell-lung-cancer-cells-to-erlotinib-in-vitro-and-in-vivo
#1
Weiwei Yu, Weiqiang Lu, Guoliang Chen, Feixiong Cheng, Hui Su, Yihua Chen, Mingyao Liu, Xiufeng Pang
BACKGROUND AND PURPOSE: Intrinsic and/or acquired resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) commonly occurs in patients with non-small-cell lung cancer (NSCLC). Here, we develop a combined therapy of histone deacetylase inhibition by a novel HDAC inhibitor, YF454A, with erlotinib to overcome EGFR-TKI resistance in NSCLC. EXPERIMENTAL APPROACH: The sensitization of erlotinib by YF454A was examined in a panel of EGFR-TKI-resistant NSCLC cell lines in vitro and two different erlotinib-resistant NSCLC xenograft mouse models in vivo...
July 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28747773/deciphering-mechanisms-of-acquired-t790m-mutation-after-egfr-inhibitors-for-nsclc-by-computational-simulations
#2
Bin Zou, Victor H F Lee, Lijiang Chen, Lichun Ma, Debby D Wang, Hong Yan
Metastatic non-small-cell lung cancer (NSCLC) with activating EGFR mutations responds very well to first and second generation tyrosine-kinase inhibitors (TKI) including gefitinib, erlotinib and afatinib. Unfortunately, drug resistance will eventually develop and about half of the cases are secondary to the emergence of acquired T790M somatic mutation. In this work, we prospectively recruited 68 patients with metastatic EGFR-mutated NSCLC who have developed progressive disease after first-line TKI with or without subsequent TKI and/or other systemic therapy...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747569/acquisition-of-the-t790m-resistance-mutation-during-afatinib-treatment-in-egfr-tyrosine-kinase-inhibitor-na%C3%A3-ve-patients-with-non-small-cell-lung-cancer-harboring-egfr-mutations
#3
Kentaro Tanaka, Kaname Nosaki, Kohei Otsubo, Koichi Azuma, Shinya Sakata, Hiroshi Ouchi, Ryotaro Morinaga, Hiroshi Wataya, Akiko Fujii, Noriaki Nakagaki, Nobuko Tsuruta, Masafumi Takeshita, Eiji Iwama, Taishi Harada, Yoichi Nakanishi, Isamu Okamoto
The T790M secondary mutation of the epidermal growth factor receptor (EGFR) gene accounts for 50% to 60% of cases of resistance to the first-generation EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. The prevalence of T790M in EGFR mutation-positive patients who acquire resistance to the irreversible, second-generation EGFR-TKI afatinib has remained unclear, however. We here determined the frequency of T790M acquisition at diagnosis of progressive disease in patients with EGFR-mutated non-small cell lung cancer (NSCLC) treated with afatinib as first-line EGFR-TKI...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28746769/regulation-of-spindle-and-kinetochore-associated-protein-1-by-antitumor-mir-10a-5p-in-renal-cell-carcinoma
#4
Takayuki Arai, Atsushi Okato, Satoko Kojima, Tetsuya Idichi, Keiichi Koshizuka, Akira Kurozumi, Mayuko Kato, Kazuto Yamazaki, Yasuo Ishida, Yukio Naya, Tomohiko Ichikawa, Naohiko Seki
Analysis of our original microRNA (miRNA) expression signature of patients with advanced renal cell carcinoma (RCC) showed that microRNA-10a-5p (miR-10a-5p) was significantly downregulated in RCC specimens. The aims of this study were to investigate the antitumor roles of miR-10a-5p and the novel cancer networks regulated by this miRNA in RCC cells. Downregulation of miR-10a-5p was confirmed in RCC tissues and RCC tissues from patients treated with tyrosine kinase inhibitors (TKIs). Ectopic expression of miR-10a-5p in RCC cell lines (786-O and A498 cells) inhibited cancer cell migration and invasion...
July 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28745320/surfactant-protein-d-inhibits-activation-of-non-small-cell-lung-cancer-associated-mutant-egfr-and-affects-clinical-outcomes-of-patients
#5
Y Umeda, Y Hasegawa, M Otsuka, S Ariki, R Takamiya, A Saito, Y Uehara, H Saijo, K Kuronuma, H Chiba, H Ohnishi, Y Sakuma, H Takahashi, Y Kuroki, M Takahashi
Tyrosine kinase inhibitor (TKI)-sensitive and TKI-resistant mutations of epidermal growth factor receptor (EGFR) are associated with lung adenocarcinoma. EGFR mutants were previously shown to exhibit ligand-independent activation. We have previously demonstrated that pulmonary surfactant protein D (SP-D, SFTPD) suppressed wild-type EGFR signaling by blocking ligand binding to EGFR. We herein demonstrate that SFTPD downregulates ligand-independent signaling in cells harboring EGFR mutations such as TKI-sensitive exon 19 deletion (Ex19del) and L858R mutation as well as TKI-resistant T790M mutation, subsequently suppressing cellular growth and motility...
July 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28743421/a-review-of-regimens-combining-pemetrexed-with-an-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-in-the-treatment-of-advanced-nonsquamous-non-small-cell-lung-cancer
#6
REVIEW
James Chih-Hsin Yang, Tony Mok, Baohui Han, Mauro Orlando, Tarun Puri, Keunchil Park
Pemetrexed is a standard first-line treatment for advanced nonsquamous non-small-cell lung cancer (NSCLC), and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a standard first-line treatment for advanced nonsquamous NSCLC with activating EGFR mutations. Pemetrexed and EGFR TKIs have different mechanisms of action and minimally overlapping toxicity profiles; therefore, it is hypothesized that their combination might result in acceptable toxicity, provided that the synergistic antitumor activity observed in preclinical studies is achieved...
July 6, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28743166/second-tyrosine-kinase-inhibitor-discontinuation-attempt-in-patients-with-chronic-myeloid-leukemia
#7
Laurence Legros, Franck E Nicolini, Gabriel Etienne, Philippe Rousselot, Delphine Rea, Stéphane Giraudier, Agnès Guerci-Bresler, Françoise Huguet, Martine Gardembas, Martine Escoffre, Jean-Christophe Ianotto, Marie-Pierre Noël, Bruno R Varet, Thomas Pagliardini, Irit Touitou, Stéphane Morisset, Francois-Xavier Mahon
BACKGROUND: Several studies have demonstrated that approximately one-half of patients with chronic myeloid leukemia (CML) who receive treatment with tyrosine kinase inhibitors (TKIs) and achieve and maintain a deep molecular response (DMR) are able to successfully discontinue therapy. In patients who have a molecular relapse, a DMR is rapidly regained upon treatment re-initiation. METHODS: The authors report the results from RE-STIM, a French observational, multicenter study that evaluated treatment-free remission (TFR) in 70 patients who re-attempted TKI discontinuation after a first unsuccessful attempt...
July 25, 2017: Cancer
https://www.readbyqxmd.com/read/28743165/prognostic-factors-and-survival-outcomes-in-patients-with-chronic-myeloid-leukemia-in-blast-phase-in-the-tyrosine-kinase-inhibitor-era-cohort-study-of-477-patients
#8
Preetesh Jain, Hagop M Kantarjian, Ahmad Ghorab, Koji Sasaki, Elias J Jabbour, Graciela Nogueras Gonzalez, Rashmi Kanagal-Shamanna, Ghayas C Issa, Guillermo Garcia-Manero, Devendra Kc, Sara Dellasala, Sherry Pierce, Marina Konopleva, William G Wierda, Srdan Verstovsek, Naval G Daver, Tapan M Kadia, Gautam Borthakur, Susan O'Brien, Zeev Estrov, Farhad Ravandi, Jorge E Cortes
BACKGROUND: Outcomes in patients with chronic myeloid leukemia in blast phase (CML-BP) are historically dismal. Herein, the authors sought to analyze the characteristics, prognostic factors, and survival outcomes in patients with CML-BP in the tyrosine kinase inhibitor (TKI) era. METHODS: A total of 477 patients with CML-BP were treated with a TKI at some point during the course of their CML. Cox proportional hazard models identified characteristics that were predictive of survival...
July 25, 2017: Cancer
https://www.readbyqxmd.com/read/28742791/correlation-between-circulating-tumor-dna-levels-and-response-to-tyrosine-kinase-inhibitors-tki-treatment-in-non-small-cell-lung-cancer
#9
Zhangjing Wei, Wenyue Wang, Zitan Shu, Xue Zhou, Yanfang Zhang
BACKGROUND Clinical monitoring of EGFR-positive NSCLC patients is important to gauge treatment response. The current study addresses the usage of circulating tumor DNA (ctDNA) as a prognostic marker during treatment of first-generation TKIs. MATERIAL AND METHODS Serial samplings of peripheral blood from 200 EGFR-positive NSCLC patients were taken. Baseline ctDNA quantification was conducted by digital droplet PCR before TKI treatment was administered and compared to primary biopsies. Thereafter blood sampling at different treatment cycles were measured and assessed for its prognostic and predictive value...
July 25, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28742419/insights-into-the-management-of-chronic-myeloid-leukemia-in-resource-poor-settings-a-mexican-perspective
#10
Andrés Gomez-De-León, David Gómez-Almaguer, Guillermo J Ruiz-Delgado, Guillermo J Ruiz-Arguelles
The arrival of targeted therapy for chronic myeloid leukemia (CML) was revolutionary. However, due to the high cost of tyrosine kinase inhibitors, access to this highly effective therapy with strict monitoring strategies is limited in low to middle-income countries. In this context, following standard recommendations proposed by experts in developed countries is difficult. Areas covered: This review aims to provide an insight into the management of patients with CML living in a resource-limited setting. It addresses several issues: diagnosis, initial treatment, disease monitoring, and additional treatment alternatives including allogeneic hematopoietic stem cell transplantation...
July 25, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28742280/clinical-outcomes-in-patients-with-advanced-egfr-mutated-non-small-cell-lung-cancer-in-south-western-sydney-local-health-district
#11
P N Ding, T L Roberts, W Chua, T M Becker, J Descallar, P Y Yip, V J Bray
AIMS: We aim to describe clinical characteristics, treatment patterns and factors influencing outcomes in patients with EGFR-mutated non-small cell lung cancer (NSCLC) in SWSLHD. METHODS: Retrospective review of patients with EGFR-mutated NSCLC diagnosed between January 2010 and June 2016. RESULTS: A total of 85 EGFR-mutated NSCLC patients were identified; 80 (94%) received first line treatment with EGFR-TKI. The median follow-up was 10.7 months with a median duration of treatment of 9 months...
July 25, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28741476/squamous-transition-of-lung-adenocarcinoma-and-drug-resistance
#12
Shenda Hou, Xiangkun Han, Hongbin Ji
Studies in mouse models support an essential role of lung adenocarcinoma (ADC) to squamous cell carcinoma (SCC) transition (AST) in the development of drug resistance. Recent observations in the clinic further suggest that this type of histological transition may be responsible for resistance to tyrosine kinase inhibitor (TKI) therapy and chemotherapy in relapsed EGFR-mutant lung ADC patients. Here we summarize the current understanding of AST and drug resistance.
September 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28740693/disease-flare-after-discontinuing-gefitinib-in-a-patient-with-lung-adenocarcinoma-and-concomitant-epithelial-growth-factor-receptor-mutation-and-anaplastic-lymphoma-kinase-translocation
#13
Eun Hye Park, Hwa Young Lee, Jin Woo Kim, Chang Dong Yeo
We report on a patient with lung adenocarcinoma and a concomitant epithelial growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation who developed a disease flare after discontinuing gefitinib. A 63-year-old woman with lung adenocarcinoma and a concomitant activating EGFR mutation and ALK translocation was treated with first-line gefitinib. After 4 months, she discontinued the gefitinib due to disease progression. She was admitted to the emergency room complaining of severe dyspnea and back pain 22 days after discontinuing gefitinib...
June 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28740406/conventional-real-time-pcr-based-detection-of-t790m-using-tumor-tissue-or-blood-in-patients-with-egfr-tki-resistant-nsclc
#14
Ya-Lan Wu, Rui-Zhan Tong, Yan Zhang, Bin-Bin Hu, Ke Zheng, Zhen-Yu Ding, Feng Peng, You-Ling Gong, Yong-Mei Liu, You Lu
Blood biopsy has many advantages over tissue biopsy for diagnosing acquired T790M mutation in patients with non-small-cell lung cancer, such as being less risky and painful. New techniques with high sensitivity (eg, droplet digital PCR) show promising results during blood biopsy, but the positive rates of identification are still quite unclear. Whether there are other factors, except technology, affecting the results of blood biopsy is unclear. In this study, we used conventional amplification refractory mutation system to detect tumor tissue or blood for T790M mutation in patients clinically resistant to tyrosine kinase inhibitors...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28735814/tyrosine-kinase-inhibitors-as-modulators-of-trastuzumab-mediated-antibody-dependent-cell-mediated-cytotoxicity-in-breast-cancer-cell-lines
#15
Denis M Collins, Kathy Gately, Clare Hughes, Connla Edwards, Anthony Davies, Stephen F Madden, Kenneth J O'Byrne, Norma O'Donovan, John Crown
BACKGROUND: Trastuzumab is an anti-HER2 monoclonal antibody (mAb) therapy capable of antibody-dependent cell-mediated cytotoxicity (ADCC) and used in the treatment of HER2+ breast cancer. Through interactions with FcƴR+ immune cell subsets, trastuzumab functions as a passive immunotherapy. The EGFR/HER2-targeting tyrosine kinase inhibitor (TKI) lapatinib and the next generation TKIs afatinib and neratinib, can alter HER2 levels, potentially modulating the ADCC response to trastuzumab...
July 15, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28734822/icotinib-versus-whole-brain-irradiation-in-patients-with-egfr-mutant-non-small-cell-lung-cancer-and-multiple-brain-metastases-brain-a-multicentre-phase-3-open-label-parallel-randomised-controlled-trial
#16
Jin-Ji Yang, Caicun Zhou, Yisheng Huang, Jifeng Feng, Sun Lu, Yong Song, Cheng Huang, Gang Wu, Li Zhang, Ying Cheng, Chengping Hu, Gongyan Chen, Li Zhang, Xiaoqing Liu, Hong Hong Yan, Fen Lai Tan, Wenzhao Zhong, Yi-Long Wu
BACKGROUND: For patients with non-small-cell lung cancer (NSCLC) and multiple brain metastases, whole-brain irradiation (WBI) is a standard-of-care treatment, but its effects on neurocognition are complex and concerning. We compared the efficacy of an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), icotinib, versus WBI with or without chemotherapy in a phase 3 trial of patients with EGFR-mutant NSCLC and multiple brain metastases. METHODS: We did a multicentre, open-label, parallel randomised controlled trial (BRAIN) at 17 hospitals in China...
July 19, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28733795/early-response-of-c-reactive-protein-as-a-predictor-of-survival-in-patients-with-metastatic-renal-cell-carcinoma-treated-with-tyrosine-kinase-inhibitors
#17
Yosuke Yasuda, Kazutaka Saito, Takeshi Yuasa, Sho Uehara, Naoko Kawamura, Minato Yokoyama, Junichiro Ishioka, Yoh Matsuoka, Shinya Yamamoto, Tetsuo Okuno, Junji Yonese, Kazunori Kihara, Yasuhisa Fujii
BACKGROUND: Pretreatment C-reactive protein (CRP) has been shown to be an independent prognostic factor for metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs). We further evaluated the early response of CRP after the initiation of TKIs. METHODS: A total of 103 patients (80 men and 23 women) were treated with TKIs for mRCC from 2008-2013. Patients were divided into three groups according to their early CRP kinetics-patients whose baseline CRP levels were <10 mg/L (non-elevated), patients whose baseline CRP levels were ≥10 mg/L and had decreased by >20% at 4 weeks after the initiation of TKIs (early CRP responder), and the remaining patients (non-early CRP responder)...
July 21, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28733559/dynamics-of-egfr-mutations-in-plasma-recapitulates-the-clinical-response-to-egfr-tkis-in-nsclc-patients
#18
Liwen Xiong, Shaohua Cui, Jingyan Ding, Yun Sun, Longfu Zhang, Yizhuo Zhao, Aiqin Gu, Tianqing Chu, Huimin Wang, Hua Zhong, Xin Ye, Yi Gu, Xin Zhang, Min Hu, Liyan Jiang
OBJECTIVES: Genomic profiling using plasma cell-free DNA (cfDNA) represents a non-invasive alternative to tumor re-biopsy, which is challenging in clinical practice. The feasibility of dynamically monitoring epidermal growth factor receptor (EGFR) mutation status using serial plasma samples from non-small cell lung cancer (NSCLC) patients treated by tyrosine kinase inhibitors (TKIs) and its application in tracking clinical response and detection of resistance were investigated. PATIENTS AND METHODS: Forty-five NSCLC patients with EGFR mutation-positive pre-TKI plasma and at least two post-TKI plasma collections were recruited to this study...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28731496/prognostic-factors-for-survival-in-metastatic-renal-cell-carcinoma-patients-with-brain-metastases-receiving-targeted-therapy
#19
Ibrahim Yildiz, Ahmet Bilici, Nuri Karadurmuş, Leyla Ozer, Deniz Tural, Mehmet A Kaplan, Tülay Akman, Ibrahim V Bayoglu, Mükremin Uysal, Yaşar Yildiz, Özgür Tanriverdi, Ozan Yazici, Zeki Sürmeli, Nazim Serdar Turhal, Sevil Bavbek, Fatih Selçukbiricik, Doğan Koca, Mert Basaran
BACKGROUND: The primary objective of our study was to examine the clinical outcomes and prognosis of patients with metastatic renal cell carcinoma (mRCC) with brain metastases (BMs) receiving targeted therapy. PATIENTS AND METHODS: Fifty-eight patients from 16 oncology centers for whom complete clinical data were available were retrospectively reviewed. RESULTS: The median age was 57 years (range 30-80). Most patients underwent a nephrectomy (n = 41; 70...
July 14, 2017: Tumori
https://www.readbyqxmd.com/read/28730963/increased-expression-of-ire1%C3%AE-associates-with-the-resistant-mechanism-of-osimertinib-azd9291-resistant-non-small-cell-lung-cancer-hcc827-osir-cells
#20
Zheng-Hai Tang, Min-Xia Su, Xia Guo, Xiao-Ming Jiang, Lin Jia, Xiuping Chen, Jin-Jian Lu
BACKGROUND: Osimertinib (OSI), also known as AZD9291, is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of non-small cell lung cancer (NSCLC) patients. OBJECTIVE: Establishment of the OSI-resistant HCC827/OSIR cell line and study of its resistant mechanism. METHOD: The anti-proliferative effect was studied through MTT and colony formation assays. The protein expression was detected by Western blot assay...
July 19, 2017: Anti-cancer Agents in Medicinal Chemistry
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