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https://www.readbyqxmd.com/read/28723866/a-case-of-resistance-to-tyrosine-kinase-inhibitor-therapy-small-cell-carcinoma-transformation-concomitant-with-plasma-genotyped-t790m-positivity
#1
Yanjun Xu, Zhiyu Huang, Lei Gong, Yun Fan
Although non-small-cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations are responsive to EGFR-tyrosine kinase inhibitors, drug resistances are always inevitable. The secondary somatic EGFR threonine-methionine substitution at position 790 (T790M) mutation accounts for ∼50% of acquired resistance mechanisms. Small cell lung cancer (SCLC) transformation is a relatively rare mechanism, but has recently attracted considerable attention. The coexistence of both the mechanisms in one patient is much more scarce in clinic...
July 18, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28723342/molecular-analysis-of-circulating-free-dna-from-lung-cancer-patients-in-routine-laboratory-practice-a-cross-platform-comparison-of-three-different-molecular-methods-for-mutation-detection
#2
Stephan Bartels, Sascha Persing, Britta Hasemeier, Elisa Schipper, Hans Kreipe, Ulrich Lehmann
Cell-free DNA (cfDNA), which is isolated from blood plasma, represents a noninvasive source for the detection of mutations conferring resistance against epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small-cell lung cancer patients. In advanced disease stages, performing regular biopsies is often not possible because of the general health condition of the patients. Furthermore, a biopsy of a single tumor lesion or metastasis may not reflect the heterogeneous genotype of the tumor and its metastases...
July 16, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28722786/oncogenic-transformation-of-lung-cells-results-in-distinct-exosome-protein-profile-similar-to-the-cell-of-origin
#3
Richard J Lobb, Marcus L Hastie, Emma L Norris, Rosa van Amerongen, Jeffrey J Gorman, Andreas Möller
Lung cancer is responsible for the highest rate of cancer mortality worldwide. Lung cancer patients are often ineligible for tumour biopsies due to co-morbidities. As a result, patients may not have the most effective treatment regimens administered. Patients with mutations in the epidermal growth factor receptor (EGFR) have improved survival in response to EGFR tyrosine kinase inhibitors (TKIs). A non-invasive method of determining EGFR mutations in patients would have promising clinical applications. Exosomes have the potential to be non-invasive novel diagnostic markers in cancer...
July 19, 2017: Proteomics
https://www.readbyqxmd.com/read/28722683/comparison-of-direct-sequencing-and-amplification-refractory-mutation-system-for-detecting-epidermal-growth-factor-receptor-mutation-in-non-small-cell-lung-cancer-patients-a-systematic-review-and-meta-analysis
#4
Qi Feng, Zu-Yao Yang, Jia-Tong Zhang, Jin-Ling Tang
BACKGROUND: Direct sequencing and amplification refractory mutation system (ARMS) are commonly used to detect epidermal growth factor receptor (EGFR) mutation status in patients with non-small-cell lung cancer to inform the decision-making on tyrosine kinase inhibitors treatment. This study aimed to systematically compare the two methods in terms of the rate of detected mutations and the association of detected mutations with clinical outcomes. MATERIAL AND METHODS: PubMed, EMBASE, China National Knowledge Infrastructure (in Chinese) and Wanfang database (in Chinese) were searched to identify relevant studies...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28721808/molecular-tests-for-the-choice-of-cancer-therapy
#5
Anna P Sokolenko, Evgeny N Imyanitov
There are over a dozen of approved cancer drugs, whose administration is tailored to predictive laboratory tests. The examples include estrogen and progesterone receptor status determination for the use of endocrine therapy, HER2 assessment for the administration of HER2-targeting agents, EGFR and ALK gene testing for lung cancer treatment, BRAF analysis in melanoma, etc. While first predictive tests relied on relatively easy laboratory procedures, more recent developments require rather sophisticated assays...
July 19, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28721096/comparison-of-gefitinib-as-first-and-second-line-therapy-for-advanced-lung-adenocarcinoma-patients-with-positive-exon-21-or-19-del-epidermal-growth-factor-receptor-mutation
#6
Nishant Patel, Pingping Wu, Haijun Zhang
OBJECTIVES: Gefitinib, a tyrosine kinase inhibitor (TKI) targeting epidermal growth factor receptor (EGFR), shows excellent clinical benefit in treating advanced non-small-cell lung cancer (NSCLC). The aim of this study was to compare the efficacy and toxicity of gefitinib as first-line therapy and second-line therapy for advanced lung adenocarcinoma patients with positive exon 21 (L858R) or exon 19 deletion of EGFR mutation. METHODS: We retrospectively analyzed the clinical data of 60 EGFR-mutated advanced lung adenocarcinoma patients from July 2011 to November 2015 who have received oral gefitinib 250 mg once daily...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28721068/patients-harboring-alk-rearrangement-adenocarcinoma-after-acquired-resistance-to-crizotinib-and-transformation-to-small-cell-lung-cancer-a-case-report
#7
You-Cai Zhu, Xing-Hui Liao, Wen-Xian Wang, Chun-Wei Xu, Wu Zhuang, Li-Hua Zhong, Kai-Qi Du, Yan-Ping Chen, Gang Chen, Mei-Yu Fang
Anaplastic lymphoma kinase (ALK) rearrangement responds to ALK tyrosine kinase inhibitors (TKIs) in lung cancer. Many cases ultimately acquire resistance to crizotinib. Resistance, including ALK-dominant or ALK non-dominant, mechanisms have been described. Transformation to small-cell lung cancer is rare. Herein, we report a 49-year-old man diagnosed with adenocarcinoma, who was negative for EGFR and ALK genes as detected by reverse transcription polymerase chain reaction, and was treated with crizotinib. A new biopsy showed a small-cell lung cancer after disease progression...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28720682/reducing-artifactual-egfr-t790m-mutations-in-dna-from-formalin-fixed-paraffin-embedded-tissue-by-use-of-thymine-dna-glycosylase
#8
Hongdo Do, Ramyar Molania, Paul L Mitchell, Rita Vaiskunaite, John D Murdoch, Alexander Dobrovic
BACKGROUND: False-positive EGFR T790M mutations have been reported in formalin-fixed lung tumors, but the cause of the false positives has not been identified. The T790M mutation results from a C>T change at the cytosine of a CpG dinucleotide. The presence or absence of methylation at this cytosine has different consequences following deamination, resulting in a thymine or uracil, respectively, both of which however result in an artifactual change. Uracil-DNA glycosylase (UDG) can be used to eliminate DNA templates with uracil residues but is not active against artifactual thymines...
July 18, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28720677/synthetic-circulating-cell-free-dna-as-quality-control-materials-for-somatic-mutation-detection-in-liquid-biopsy-for-cancer
#9
Rui Zhang, Rongxue Peng, Ziyang Li, Peng Gao, Shiyu Jia, Xin Yang, Jiansheng Ding, Yanxi Han, Jiehong Xie, Jinming Li
BACKGROUND: Detection of somatic genomic alterations in tumor-derived cell-free DNA (cfDNA) in the plasma is challenging owing to the low concentrations of cfDNA, variable detection methods, and complex workflows. Moreover, no proper quality control materials are available currently. METHODS: We developed a set of synthetic cfDNA quality control materials (SCQCMs) containing spike-in cfDNA on the basis of micrococcal nuclease digestion carrying somatic mutations as simulated cfDNA and matched genomic DNA as genetic background to emulate paired tumor-normal samples in real clinical tests...
July 18, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28719349/identification-of-g2607a-mutation-in-egfr-gene-with-a-significative-rate-in-moroccan-patients-with-bladder-cancer
#10
W El Hamdani, K Hadami, M Bensaid, H El Ahanidi, A Ameur, A Filali Maltouf, M Abbar, M Attaleb, A Albouzidi, M El Mzibri
The epidermal growth factor receptor (EGFR) is involved in the regulation of several cellular processes and in the development of many human cancers. Somatic mutations of EGFR at tyrosine kinase domain have been associated with clinical response to tyrosine kinase inhibitors (TKIs) in lung cancer patients. In this study, we evaluated the frequency of point mutations in EGFR for future use of TKI in clinical treatment of bladder cancer. A total, 50 Moroccan patient specimens with bladder cancer and 48 healthy controls were analysed for EGFR mutations in the region delimiting exons 18-21 by PCR amplification and direct sequencing...
May 20, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28718011/case-series-on-the-association-between-blood-levels-and-side-effects-of-afatinib-maleate
#11
Junya Sato, Naoto Morikawa, Ryosuke Chiba, Satoru Nihei, Satoshi Moriguchi, Heisuke Saito, Kohei Yamauchi, Kenzo Kudo
PURPOSE: Afatinib maleate (AFA) is a second-generation, tyrosine kinase inhibitor (TKI) treatment for specific variants of non-small cell lung cancer exhibiting epidermal growth factor receptor (EGFR) mutations. In this study, we measured the blood AFA levels in six patients with lung cancer and investigated the association between blood levels and side effects of this drug. METHODS: The study subjects were patients who were administered AFA for non-small cell lung cancer...
July 17, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28717762/epidermal-growth-factor-receptor-mutational-status-and-brain-metastases-in-non-small-cell-lung-cancer
#12
Vijaya Raj Bhatt, Sanyo P D'Souza, Lynette M Smith, Allison M Cushman-Vokoun, Vanita Noronha, Vivek Verma, Amit Joshi, Anuradha Chougule, Nirmala Jambhekar, Anne Kessinger, Alissa Marr, Vijay Patil, Sripad D Banavali, Apar Kishor Ganti, Kumar Prabhash
INTRODUCTION: Epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancers (NSCLC) may be more common in patients with brain metastases. Previous studies, however, did not adjust for effects of confounding variables. METHODS: This retrospective study included 1,522 consecutive patients with NSCLC, whose tumors were diagnosed and tested for EGFR mutations at the University of Nebraska Medical Center (Omaha, NE) and Tata Memorial Hospital (Mumbai, India)...
June 2017: Journal of Global Oncology
https://www.readbyqxmd.com/read/28717712/egfr-mutations-in-latinos-from-the-united-states-and-latin-america
#13
Ariel Lopez-Chavez, Anish Thomas, Moses O Evbuomwan, Liqiang Xi, Guinevere Chun, Tatiana Vidaurre, Oscar Arrieta, George Oblitas, Ana Belen Oton, Alejandro R Calvo, Arun Rajan, Mark Raffeld, Seth M Steinberg, Lorena Arze-Aimaretti, Giuseppe Giaccone
PURPOSE: Epidermal growth factor receptor (EGFR) mutations confer sensitivity to EGFR tyrosine kinase inhibitors in patients with advanced non-small-cell lung cancer (NSCLC). There are limited and conflicting reports on the frequency of EGFR mutations in Latinos. PATIENTS AND METHODS: Samples from 642 patients with NSCLC from seven institutions in the United States and Latin America were assessed for EGFR mutations (exons 18 to 21) at Clinical Laboratory Improvement Amendments-certified central laboratories...
October 2016: Journal of Global Oncology
https://www.readbyqxmd.com/read/28717660/a-novel-molecular-diagnostics-platform-for-somatic-and-germline-precision-oncology
#14
Rubén Cabanillas, Marta Diñeiro, David Castillo, Patricia C Pruneda, Cristina Penas, Guadalupe A Cifuentes, Álvaro de Vicente, Noelia S Durán, Rebeca Álvarez, Gonzalo R Ordóñez, Juan Cadiñanos
BACKGROUND: Next-generation sequencing (NGS) opens new options in clinical oncology, from therapy selection to genetic counseling. However, realization of this potential not only requires succeeding in the bioinformatics and interpretation of the results, but also in their integration into the clinical practice. We have developed a novel NGS diagnostic platform aimed at detecting (1) somatic genomic alterations associated with the response to approved targeted cancer therapies and (2) germline mutations predisposing to hereditary malignancies...
July 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28717642/lung-adenocarcinoma-patients-of-young-age-have-lower-egfr-mutation-rate-and-poorer-efficacy-of-egfr-tyrosine-kinase-inhibitors
#15
Shang-Gin Wu, Yih-Leong Chang, Chong-Jen Yu, Pan-Chyr Yang, Jin-Yuan Shih
Patients aged ≤50 years are rarely diagnosed with nonsmall cell lung cancer. We conducted a retrospective cohort study to understand the mutation status of EGFR and the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in young Asian patients with lung adenocarcinoma. We collected tumour specimens and malignant pleural effusions from lung adenocarcinoma patients from June 2005 to April 2014, recorded their clinical demographic data, and analysed EGFR mutations by reverse transcriptase PCR...
July 2017: ERJ Open Research
https://www.readbyqxmd.com/read/28717102/human-lung-adenocarcinoma-cells-with-an-egfr-mutation-are-sensitive-to-non-autophagic-cell-death-induced-by-zinc-oxide-and-aluminium-doped-zinc-oxide-nanoparticles
#16
Kuan-Jen Bai, Kai-Jen Chuang, Chih-Ming Ma, Ta-Yuan Chang, Hsiao-Chi Chuang
Lung cancer, mostly non-small cell lung cancer (NSCLC), is the leading cause of cancer deaths; however, efficient treatments for NSCLC remain insufficient. The objective of this study was to investigate the effects of an epidermal growth factor receptor (EGFR) mutation on autophagic cell death in human lung adenocarcinoma cells by 20-nm zinc oxide nanoparticles (ZnONP20) and aluminum-doped ZnONPs (Al-ZnONP20). Two types of human lung adenocarcinoma cells were used throughout the study: wild-type EGFR A549 cells and EGFR-mutated CL1-5 cells...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28716728/cytochrome-p450-3a-selectively-affects-the-pharmacokinetic-interaction-between-erlotinib-and-docetaxel-in-rats
#17
Xuan Qin, Jian Lu, Peili Wang, Peipei Xu, Mingyao Liu, Xin Wang
Erlotinib as a first-line drug is used in non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations, while resistance to this drug will occur after several years of treatment. Therefore, the microtubule disturber docetaxel is introduced as combined regimen in clinical trials. This report investigated the potentials and mechanisms of drug-drug interaction (DDI) between erlotinib and docetaxel using wild type (WT) and Cyp3a1/2 knockout (KO) rats. The erlotinib O-demethylation and docetaxel hydroxylation reactions in the absence or the presence of another drug were analyzed in vitro via the assay of rat liver microsomes...
July 14, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28712979/clinical-implications-of-the-t790m-mutation-in-disease-characteristics-and-treatment-response-in-patients-with-epidermal-growth-factor-receptor-egfr-mutated-non-small-cell-lung-cancer%C3%A2-nsclc
#18
Daria Gaut, Myung Shin Sim, Yuguang Yue, Brian R Wolf, Phillip A Abarca, James M Carroll, Jonathan W Goldman, Edward B Garon
BACKGROUND: The secondary T790M mutation accounts for more than 50% of acquired tyrosine kinase inhibitor (TKI) resistance in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). Recent reports suggest this resistance mutation may be more common among patients with longer progression-free survival (PFS) on first-line TKI therapy, but much is still unknown. MATERIALS AND METHODS: Our group collected medical records from patients who underwent a biopsy for T790M mutation testing while screening for clinical trials involving the drug rociletinib (CO-1686), a T790M mutation-specific TKI...
June 20, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28712427/depression-inflammation-and-epidermal-growth-factor-receptor-egfr-status-in-metastatic-non-small-cell-lung-cancer-a-pilot-study
#19
Jamie M Jacobs, Lara Traeger, Justin Eusebio, Naomi M Simon, Lecia V Sequist, Joseph A Greer, Jennifer S Temel, William F Pirl
OBJECTIVE: Patients with stage IV non-small cell lung cancer (NSCLC) have high risk for depressive symptoms and major depressive disorder (MDD); however, those with epidermal growth factor receptor (EGFR) mutations may have decreased risk. The biological underpinning of this relationship is unknown. We examined differences in depression severity and MDD in patients with newly diagnosed stage IV NSCLC based on EGFR mutation status, and examined proinflammatory cytokines and growth factors known to play a role in cancer progression and depression...
August 2017: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/28712102/precision-medicine-in-metastatic-colorectal-cancer-relevant-carcinogenic-pathways-and-targets-part-2-approaches-beyond-first-line-therapy-and-novel-biologic-agents-under-investigation
#20
REVIEW
Benjamin A Weinberg, Marion L Hartley, Mohamed E Salem
A frequent quandary for oncologists is the selection of chemotherapy and biologic therapy for patients with metastatic colorectal cancer in second-line and higher treatment settings. While not approved by the US Food and Drug Administration (FDA) in the first-line setting, the vascular endothelial growth factor (VEGF)-targeting agents ziv-aflibercept and ramucirumab are appropriate treatment options in the second-line setting, as is continuation of first-line bevacizumab. Tumor RAS mutational status is helpful to determine which patients may benefit from epidermal growth factor receptor (EGFR)-directed therapies, and other novel biomarkers (BRAF, HER2, and mismatch repair deficiency) allow us to select patients who may benefit from biologic therapies that are FDA-approved for other malignancies...
July 15, 2017: Oncology (Williston Park, NY)
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