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Egfr-tki treatment for lung cancer

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https://www.readbyqxmd.com/read/28093061/polyphyllin-ii-restores-sensitization-of-the-resistance-of-pc-9-zd-cells-to-gefitinib-by-a-negative-regulation-of-the-pi3k-akt-mtor-signaling-pathway
#1
Ruzhen Zheng, Hao Jiang, Jinhui Li, Xinge Liu, Hongwei Xu
: EGFR tyrosine kinase inhibitors (TKIs) are widely used for advanced non-small cell lung cancer (NSCLC) patients with a sensitizing EGFR mutation and provide a promising treatment strategy. However, acquired resistance to EGFR-TKIs restrict their application. The mechanisms underlying acquired resistance to TKIs have been explored and Phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway plays a very important role in NSCLC development as well as EGFR-TKI resistance. Polyphyllin II(PP II) is the main steroidal saponin constituent which derives from the root of Paris polychylia...
December 13, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28089159/immunohistochemistry-for-egfr-mutation-detection-in-non-small-cell-lung-cancer
#2
Nina Turnšek Hitij, Izidor Kern, Aleksander Sadikov, Lea Knez, Karmen Stanič, Matjaž Zwitter, Tanja Cufer
INTRODUCTION: The sensitivity and specificity of immunohistochemistry (IHC) was compared with the standard polymerase chain reaction (PCR)-based method for detecting common activating epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC). Additionally, we evaluated predictive value of IHC EGFR mutation-positive status for EGFR tyrosine kinase inhibitor (TKI) treatment outcome and estimated cost-effectiveness for the upfront IHC testing. METHODS: The trial included 79 consecutive EGFR mutation-positive and 29 EGFR mutation-negative NSCLC cases diagnosed with reflex PCR-based testing...
December 2, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28088511/brief-report-egfr-l858m-l861q-cis-mutations-confer-selective-sensitivity-to-afatinib
#3
Jamie A Saxon, Lynette M Sholl, Pasi A Jänne
INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have been developed to treat patients with epidermal growth factor receptor (EGFR)-mutant lung cancers. However, the therapeutic efficacy of TKIs in patients with uncommon EGFR mutations remains unclear. METHODS: Next-generation sequencing was performed on a patient's lung adenocarcinoma tumor sample, revealing rare combined in cis (on the same allele) EGFR mutations. Stable Ba/F3 and NIH-3T3 cell lines harboring the mutations were established to investigate the effect of first, second, and third generation EGFR TKIs on cell proliferation by MTS assay and EGFR phosphorylation by Western blotting...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28079142/the-prognostic-role-of-egfr-tkis-for-patients-with-advanced-non-small-cell-lung-cancer
#4
Dan Zhao, Xuejing Chen, Na Qin, Dan Su, Lijuan Zhou, Quan Zhang, Xi Li, Xinyong Zhang, Mulan Jin, Jinghui Wang
Clinical trials have shown that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) did not improve the survival of patients with EGFR-mutated non-small cell lung cancer (NSCLC) because of the high crossover of treatments. Realistically, the role of EGFR-TKIs in NSCLC with mutated EGFR is not well known. We retrospectively analysed data from patients with recurrent or metastatic NSCLC. Clinical prognostic factors were identified by Cox proportional hazards modelling. Among 503 patients, the median overall survival (OS) for all of patients was 11...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28076323/clinical-outcome-of-tyrosine-kinase-inhibitors-alone-or-combined-with-radiotherapy-for-brain-metastases-from-epidermal-growth-factor-receptor-egfr-mutant-non-small-cell-lung-cancer-nsclc
#5
Qianqian Zhu, Yanan Sun, Yingying Cui, Ke Ye, Chengliang Yang, Daoke Yang, Jie Ma, Xiao Liu, Jinming Yu, Hong Ge
This study compared treatment outcomes between TKI monotherapy and TKI administration combined with brain radiotherapy (TKI + RT) in 133 non-small cell lung cancer (NSCLC) patients with brain metastasis (BM). We also evaluated the association of different epidermal growth factor receptor (EGFR) mutation subtypes with treatment outcome. To screen for potential variables affecting cranial progression free survival (PFS) and overall survival (OS), we performed univariate and multivariate analysis based on Cox proportional-hazards models...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28073786/phase-1-study-of-twice-weekly-pulse-dose-and-daily-low-dose-erlotinib-as-initial-treatment-for-patients-with-egfr-mutant-lung-cancers
#6
H A Yu, C Sima, D Feldman, L L Liu, B Vaitheesvaran, J Cross, C M Rudin, M G Kris, W Pao, F Michor, G J Riely
BACKGROUND: Patients with EGFR-mutant lung cancers treated with EGFR tyrosine kinase inhibitors (TKIs) develop clinical resistance, most commonly with acquisition of EGFR T790M. Evolutionary modeling suggests that a schedule of twice weekly pulse and daily low-dose erlotinib may delay emergence of EGFR T790M. Pulse dose erlotinib has superior central nervous system (CNS) penetration and may result in superior CNS disease control. METHODS: We evaluated toxicity, pharmacokinetics, and efficacy of twice weekly pulse and daily low-dose erlotinib...
October 25, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28061471/transformation-to-small-cell-carcinoma-as-an-acquired-resistance-mechanism-to-azd9291-a-case-report
#7
Lin Li, Hui Wang, Chao Li, Zheng Wang, Ping Zhang, Xu Yan
AZD9291, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), benefits patients with T790M mutant non-small-cell lung cancer who fail treatment with first-generation EGFR TKIs. Acquisition of resistance to AZD9291 occurs inevitable and mechanisms need to be explored. We reported an advanced lung adenocarcinoma female with EGFR exon19 deletion treated on AZD9291 after failure of erlotinib and chemotherapy. Disease progressed again after 6 months' treatment of AZD9291 with hepatic metastasis...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28061461/estimation-of-cell-free-circulating-egfr-mutation-concentration-predicts-outcomes-in-nsclc-patients-treated-with-egfr-tkis
#8
Yan-Juan Zhu, Hai-Bo Zhang, Yi-Hong Liu, Fu-Li Zhang, Ya-Zhen Zhu, Yong Li, Jian-Ping Bai, Li-Rong Liu, Yan-Chun Qu, Xin Qu, Xian Chen, Yan Li, Guang-Juan Zheng
Detection of circulating tumor DNA using droplet digital polymerase chain reaction (ddPCR) is a highly-sensitive, minimally invasive alternative to serial biopsies for assessment and management of cancer. We used ddPCR to assess the utility of measuring plasma concentrations of common epidermal growth factor receptor (EGFR) mutations (L858R, exon 19 deletion, and T790M) in 57 non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). High baseline plasma EGFR mutation (pEGFRmut) concentrations were associated with shorter progression-free survival (8...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28031837/carcinomatous-pleuritis-and-pericarditis-accompanied-by-pulmonary-tuberculosis
#9
Munechika Hara, Shin-Ichiro Iwakami, Naohisa Matsumoto, Taichi Miyawaki, Ryo Wada, Kazuhisa Takahashi
Although both lung cancer and pulmonary tuberculosis (TB) commonly occur in clinical practice, little attention has been paid to their coexistence. A 62-year-old female was admitted with acute dyspnoea secondary to cardiac tamponade. During her admission, a mass lesion harbouring air bronchograms in the right upper lobe rapidly increased in size. Surgical lung, pericardial, and pleural specimens yielded TB from a nodule in the right upper lobe and lung adenocarcinoma from the pericardium and pleura. Anti-tuberculous therapy was administered and gefitinib was subsequently started after the positive identification of epidermal growth factor receptor (EGFR) mutation (exon 19 deletion)...
November 2016: Respirology Case Reports
https://www.readbyqxmd.com/read/28029530/survival-of-asian-females-with-advanced-lung-cancer-in-the-era-of-tyrosine-kinase-inhibitor-therapy
#10
Daniel J Becker, Juan P Wisnivesky, Michael L Grossbard, Abraham Chachoua, D Ross Camidge, Benjamin P Levy
INTRODUCTION: We examined the effect of access to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy on survival for Asian female (AF) EGFR mutation-enriched patients with advanced lung adenocarcinoma. MATERIALS AND METHODS: We used the Surveillance Epidemiology and End Results database to study patients with stage IV lung adenocarcinoma diagnosed from 1998 to 2012. We compared survival (lung cancer-specific survival [LCSS] and overall survival) between AFs and non-Asian males (NAMs), an EGFR mutation-enriched and EGFR mutation-unenriched population, respectively, with a diagnosis in the pre-EGFR TKI (1998-2004) and EGFR TKI (2005-2012) eras...
October 5, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28012496/an-autopsy-case-of-bronchiolitis-obliterans-as-a-previously-unrecognized-adverse-event-of-afatinib-treatment
#11
Nobuhiro Kanaji, Yoichi Chiba Md PhD, Akira Sato Md PhD, Masaki Ueno Md PhD, Akira Tadokoro Md PhD, Nobuyuki Kita Md, Tomoya Ishii Md PhD, Naoki Watanabe Md, Norimitsu Kadowaki Md PhD, Shuji Bandoh Md PhD
Interstitial lung disease is a well-known pulmonary adverse event that occurs during epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy and results in restrictive ventilatory dysfunction. However, obstructive changes such as those associated with bronchiolitis obliterans (BO) have never been reported as adverse events resulting from the use of any approved EGFR-TKI. This report documents an autopsy case of BO that developed during afatinib treatment for adenocarcinoma of the lung...
January 2017: Respiratory Investigation
https://www.readbyqxmd.com/read/28007627/clinical-outcome-of-alk-positive-non-small-cell-lung-cancer-nsclc-patients-with-de-novo-egfr-or-kras-co-mutations-receiving-tyrosine-kinase-inhibitors-tki
#12
Sabine Schmid, Oliver Gautschi, Sacha Rothschild, Michael Mark, Patrizia Froesch, Dirk Klingbiel, Hermann Reichegger, Wolfram Jochum, Joachim Diebold, Früh Martin
BACKGROUND: Non-small cell lung cancer (NSCLC) with de novo anaplastic lymphoma kinase (ALK) rearrangements and epidermal growth factor receptor (EGFR) or Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations co-occur very rarely. Outcomes with tyrosine kinase inhibitors (TKIs) in these patients (pts) are poorly understood. METHODS: Outcomes of pts with metastatic NSCLC de novo co- alterations of ALK/EGFR or ALK/KRAS detected by FISH (ALK) and sequencing (EGFR/KRAS) from six Swiss centres were analysed...
December 19, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28007626/risk-of-treatment-related-toxicities-from-egfr-tyrosine-kinase-inhibitors-a-meta-analysis-of-clinical-trials-of-gefitinib-erlotinib-and-afatinib-in-advanced-egfr-mutated-non-small-cell-lung-cancer
#13
Pei Ni Ding, Sarah J Lord, Val Gebski, Matthew Links, Victoria Bray, Richard J Gralla, James Chih-Hsin Yang, Chee Khoon Lee
BACKGROUND: Gefitinib, erlotinib, and afatinib are tyrosine kinase inhibitors (TKIs) used for treatment of advanced epidermal growth factor receptor (EGFR) mutated non-small-cell lung cancer (NSCLC). Estimating differences in toxicity between these EGFR-TKIs is important for personalizing treatment. METHODS: We performed a meta-analysis of randomized trials that compared EGFR-TKI against chemotherapy or placebo. We extracted data from the EGFR-TKI arm for indirect comparisons to estimate the relative risk of toxic death, grade 3-4 (G3/4) adverse events (AEs) and treatment discontinuation due to AE for each EGFR-TKI...
December 19, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28003764/correlation-between-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-efficacy-and-circulating-tumor-cell-levels-in-patients-with-advanced-non-small-cell-lung-cancer
#14
Wenjie He, Wenhui Li, Bo Jiang, Li Chang, Congguo Jin, Changlin Tu, Yunfen Li
OBJECTIVE: The aim of this study was to investigate the correlation between the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and circulating tumor cell (CTC) levels in patients with advanced non-small cell lung cancer (NSCLC). The efficacy of EGFR-TKIs in reducing CTC counts in patients with advanced NSCLC was studied. PATIENTS AND METHODS: A total of 66 patients with advanced NSCLC were enrolled and divided into two groups (those with high CTC counts and those with low CTC counts) based on the patients' median CTC counts...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28003335/the-ras-related-gtpase-rhob-confers-resistance-to-egfr-tyrosine-kinase-inhibitors-in-non-small-cell-lung-cancer-via-an-akt-dependent-mechanism
#15
Olivier Calvayrac, Julien Mazières, Sarah Figarol, Claire Marty-Detraves, Isabelle Raymond-Letron, Emilie Bousquet, Magali Farella, Estelle Clermont-Taranchon, Julie Milia, Isabelle Rouquette, Nicolas Guibert, Amélie Lusque, Jacques Cadranel, Nathalie Mathiot, Ariel Savina, Anne Pradines, Gilles Favre
Although lung cancer patients harboring EGFR mutations benefit from treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKI), most of them rapidly relapse. RHOB GTPase is a critical player in both lung carcinogenesis and the EGFR signaling pathway; therefore, we hypothesized that it could play a role in the response to EGFR-TKI In a series of samples from EGFR-mutated patients, we found that low RHOB expression correlated with a good response to EGFR-TKI treatment while a poor response correlated with high RHOB expression (15...
December 21, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28002980/targeting-the-egfr-t790m-mutation-in-non-small-cell-lung-cancer
#16
Nicola Normanno, Monica Rosaria Maiello, Nicoletta Chicchinelli, Alessia Iannaccone, Claudia Esposito, Rossella De Cecio, Amelia D'alessio, Antonella De Luca
The presence of activating mutations of the epidermal growth factor receptor (EGFR) is predictive of response to first- and second-generation tyrosine kinase inhibitors (TKIs) in patients with advanced non-small-cell lung cancer (NSCLC). However, patients that initially respond to these drugs inexorably become resistant. The T790M mutation in the exon 20 of the EGFR is the main mechanism of resistance to EGFR TKIs occurring in over 50% of the cases. Third generation EGFR TKIs have been shown to be active in patients who progressed after TKI treatment and carry the T790M mutation...
December 23, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28000387/a-comparison-of-ddpcr-and-arms-for-detecting-egfr-t790m-status-in-ctdna-from-advanced-nsclc-patients-with%C3%A2-acquired-egfr-tki-resistance
#17
Wenxian Wang, Zhengbo Song, Yiping Zhang
A sensitive and convenient method for detecting epidermal growth factor receptor (EGFR) T790M mutations from circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI resistance would be desirable to direct patient sequential treatment strategy. A comparison of two platforms for detecting EGFR mutations in plasma ctDNA was undertaken. Plasma samples and tumor samples were collected from patients with acquired EGFR-TKI resistance in Zhejiang Cancer Hospital from December 2014 to December 2015...
December 20, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27989877/chinese-herbal-medicine-fuzheng-kang-ai-decoction-sensitized-the-effect-of-gefitinib-on-inhibition-of-human-lung-cancer-cells-through-inactivating-pi3-k-akt-mediated-suppressing-muc1-expression
#18
Longmei Li, SuMei Wang, Fang Zheng, WanYin Wu, Swei Sunny Hann
ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicine (CHM) Fuzheng Kang-Ai (FZKA for short) decoction has been used as adjuvant treatment strategies in lung cancer patients for decades. However, the molecular mechanism underlying the therapeutic potential especially in sensitizing the effect of EGFR-TKI gefitinib has not been well elucidated. MATERIALS AND METHODS: Cell viability was detected by MTT assay. Cell cycle distribution was detected by flow cytometry...
October 28, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27987577/coexistence-of-p16-cdkn2a-homozygous-deletions-and-activating-egfr-mutations-in-lung-adenocarcinoma-patients-signifies-a-poor-response-to-egfr-tkis
#19
Juhong Jiang, Yingying Gu, Jing Liu, Ruibin Wu, Lin Fu, Jin Zhao, Yubao Guan
OBJECTIVES: Activating mutations in the epidermal growth factor receptor (EGFR) are strongly predictive of EGFR-tyrosine kinase inhibitor (TKI) activity in non-small cell lung cancer (NSCLC). However, primary resistance to EGFR-TKIs occurs in approximately 20-30% of NSCLC patients with EGFR mutations. The goal of this study was to determine whether p16/CDKN2A homozygous deletion (HD) is associated with primary resistance to EGFR-TKIs in lung adenocarcinoma patients with EGFR activating mutations...
December 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27980215/guide-to-detecting-epidermal-growth-factor-receptor-egfr-mutations-in-ctdna-of-patients-with-advanced-non-small-cell-lung-cancer
#20
REVIEW
Nicola Normanno, Marc G Denis, Kenneth S Thress, Marianne Ratcliffe, Martin Reck
Cancer treatment is evolving towards therapies targeted at specific molecular abnormalities that drive tumor growth. Consequently, to determine which patients are eligible, accurate assessment of molecular aberrations within tumors is required. Obtaining sufficient tumor tissue for molecular testing can present challenges; therefore, circulating free tumor-derived DNA (ctDNA) found in blood plasma has been proposed as an alternative source of tumor DNA. The diagnostic utility of ctDNA for the detection of epidermal growth factor receptor (EGFR) mutations harbored in tumors of patients with advanced non-small-cell lung cancer (NSCLC) is supported by the results of several large studies/meta-analyses...
December 12, 2016: Oncotarget
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