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https://www.readbyqxmd.com/read/29790124/colorectal-cancer-why-does-side-matter
#1
Claire Gallois, Simon Pernot, Aziz Zaanan, Julien Taieb
Colorectal cancer (CRC) is a heterogeneous disease, and the search for clinical and molecular prognostic and predictive factors is thus necessary to better tailor each individual patient's management. Primary tumor location (PTL) seems to act as a master prognostic factor pooling different clinical, pathological, and molecular poor prognostic factors. In fact, right-sided (RS) CRC patients are more frequently female and elderly with microsatellite unstable, BRAF mutated, CpG island methylator phenotype (CIMP)-high, poorly differentiated tumors, compared to left-sided (LS) CRC patients...
May 22, 2018: Drugs
https://www.readbyqxmd.com/read/29789542/rnf25-promotes-gefitinib-resistance-in-egfr-mutant-nsclc-cells-by-inducing-nf-%C3%AE%C2%BAb-mediated-erk-reactivation
#2
Jung Hee Cho, Yeon-Mi You, Young Il Yeom, Dong Chul Lee, Bo-Kyung Kim, Misun Won, Byoung Chul Cho, Minho Kang, Seulki Park, Suk-Jin Yang, Jang Seong Kim, Jung-Ae Kim, Kyung Chan Park
Non-small cell lung cancer (NSCLC) patients with EGFR mutations initially respond well to EGFR tyrosine kinase inhibitors (TKIs) but eventually exhibit acquired or innate resistance to the therapies typically due to gene mutations, such as EGFR T790M mutation or a second mutation in the downstream pathways of EGFR. Importantly, a significant portion of NSCLC patients shows TKI resistance without any known mechanisms, calling more comprehensive studies to reveal the underlying mechanisms. Here, we investigated a synthetic lethality with gefitinib using a genome-wide RNAi screen in TKI-resistant EGFR-mutant NSCLC cells, and identified RNF25 as a novel factor related to gefitinib resistance...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29789220/adaura-phase-iii-double-blind-randomized-study-of-osimertinib-versus-placebo-in-egfr-mutation-positive-early-stage-nsclc-after-complete-surgical-resection
#3
Yi-Long Wu, Roy S Herbst, Helen Mann, Yuri Rukazenkov, Marcelo Marotti, Masahiro Tsuboi
INTRODUCTION: Currently, the role of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as adjuvant therapy for early-stage non-small-cell lung cancer after complete surgical tumor resection remains under investigation. We present the rationale and study design for the ADAURA (ClinicalTrials.gov identifier, NCT02511106) trial, a multicenter, double-blind, randomized, placebo-controlled study. PATIENTS AND METHODS: Study entry will be limited to adults aged ≥ 18 years (and in Japan and Taiwan, age ≥ 20 years) with primary nonsquamous stage IB-IIIA non-small-cell lung cancer with central confirmation of an EGFR exon 19 deletion or L858R mutation...
May 1, 2018: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29789021/epidermal-growth-factor-receptor-egfr-t790m-mutation-identified-in-plasma-indicates-failure-sites-and-predicts-clinical-prognosis-in-non-small-cell-lung-cancer-progression-during-first-generation-tyrosine-kinase-inhibitor-therapy-a-prospective-observational
#4
Shirong Zhang, Lucheng Zhu, Bing Xia, Enguo Chen, Qiong Zhao, Xiaochen Zhang, Xueqin Chen, Xufeng Chen, Shenglin Ma
INTRODUCTION: Plasma circulating tumor DNA (ctDNA) is an ideal approach to detecting the epidermal growth factor receptor (EGFR) T790M mutation, which is a major mechanism of resistance to first-generation EGFR-tyrosine kinase inhibitor (TKI) therapy. The present study aimed to explore the association of ctDNA-identified T790M mutation with disease failure sites and clinical prognosis in non-small cell lung cancer (NSCLC) patients. METHODS: Patients who progressed on first-generation TKIs were categorized into failure site groups of chest limited (CF), brain limited (BF) and other (OF)...
May 22, 2018: Cancer communications
https://www.readbyqxmd.com/read/29788985/establishment-of-lung-cancer-patient-derived-xenograft-models-and-primary-cell-lines-for-lung-cancer-study
#5
Yanan Jiang, Jimin Zhao, Yi Zhang, Ke Li, Tiepeng Li, Xinhuan Chen, Simin Zhao, Song Zhao, Kangdong Liu, Ziming Dong
BACKGROUND: The overall 5-year survival rate of lung cancer is about 15% even with therapeutic drugs like tyrosine kinase inhibitors. Ideal models are urgently needed for exploring mechanisms and finding new drugs. Patient-derived xenografts (PDX) models and primary cells are both used to screen therapeutic regimens for cancer. However, PDX models and primary cells from the same patient are difficult to establish. Their consistency to the original tumor tissue is not well studied. METHODS: 31 lung cancer patient tissues were procured to establish the lung cancer PDX models and primary cell lines...
May 22, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29788743/novel-insights-into-transcriptional-dysregulation-in-colorectal-cancer
#6
Y Feodorova, D Tashkova, I Koev, A Todorov, G Kostov, K Simitchiev, V Belovejdov, R Dimov, V Sarafian
Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Although CRC has been comprehensively characterized at the molecular level, the tumor heterogeneity hinders the identification of reliable diagnostic, prognostic and predictive biomarkers. Molecular stratification of CRC is based on prevalent gene mutations and transcription profiles but its significance for clinical practice remains obscure. Indeed, activating mutations in the genes KRAS, NRAS and BRAF are the only predictive biomarkers for anti-EGFR antibody therapy routinely tested the clinic for advanced stages of CRC...
March 14, 2018: Neoplasma
https://www.readbyqxmd.com/read/29788737/diagnosis-for-carcinoma-of-unknown-primary-site-with-the-aid-of-simple-pcr-tests-a-single-center-experience
#7
E Suspitsin, G Yanus, E Imyanitov
This study was aimed to incorporate PCR testing in the determination of organ/tissue origin for cancers of unknown primary site (CUP). We developed a PCR panel consisting of 7 expression markers (CDX2, CDH17, SPB, UGRP, MAM, LPB, TG) and 2 genes frequently mutated in cancer (KRAS and BRAF). The expression tests were intentionally interpreted in a non-quantitative way, i.e. classified tumors either as positive or negative expressors. While applying these tests to 135 cancers belonging to 8 common types of adenocarcinomas (AdCa), we observed that this panel was capable to clearly discriminate between gastrointestinal vs...
March 14, 2018: Neoplasma
https://www.readbyqxmd.com/read/29787863/validity-of-targeted-next-generation-sequencing-in-routine-care-for-identifying-clinically-relevant-molecular-profiles-in-non-small-cell-lung-cancer-results-of-a-2-year-experience-on-1-343-samples
#8
Antoine Legras, Marc Barritault, Anne Tallet, Elizabeth Fabre, Alice Guyard, Bastien Rance, William Digan, Nicolas Pecuchet, Etienne Giroux-Leprieur, Catherine Julie, Stéphane Jouveshomme, Véronique Duchatelle, Véronique Giraudet, Laure Gibault, Alain Cazier, Jean Pastre, Françoise LE Pimpec-Barthes, Pierre Laurent-Puig, Hélène Blons
Theranostic assays are based on single gene testing but the ability of next-generation sequencing (NGS) to interrogate numerous genetic alterations will progressively replace single gene assays. Although NGS was evaluated to screen for theranostic mutations, its usefulness in clinical practice on large series of samples remains to be demonstrated. NGS performance was assessed following guidelines. TaqMan probes and NGS were compared for their ability to detect EGFR and KRAS mutations and NGS mutation profiles were analyzed on a large series of NSCLC (n=1,343)...
May 19, 2018: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29787277/targeting-of-egfr-vegfr2-and-akt-by-engineered-dual-drug-encapsulated-mesoporous-silica-gold-nanoclusters-sensitizes-tamoxifen-resistant-breast-cancer
#9
Bn Prashanth Kumar, Nagaprasad Puvvada, Shashi Rajput, Siddik Sarkar, Madhusudan Kr Mahto, Murali M Yallapu, Amita Pathak, Luni Emdad, Swadesh K Das, Rui L Reis, Subhas C Kundu, Paul B Fisher, Mahitosh Mandal
Tamoxifen has improved overall disease-free survival and reduced mortality rates in cancer patients. However, breast cancer patients often fail to respond to tamoxifen therapy due to the development of a drug-resistant phenotype. Functional analysis and molecular studies suggest that protein mutation and dysregulation of survival signaling molecules such as epidermal growth factor receptor, vascular endothelial growth factor receptor 2 and Akt contribute to tamoxifen resistance. Various strategies, including combinatorial therapies, show to chemo-sensitize tamoxifen-resistant cancers...
May 22, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29784736/targeted-therapy-for-patients-with-metastatic-non-small-cell-lung-cancer
#10
Karen L Reckamp
Molecular testing is recommended for initial diagnosis in patients with non-small cell lung cancer (NSCLC), according to the updated NCCN Guidelines, because targeted therapies are available that can improve patient outcomes. Targeted therapies are currently approved for EGFR mutations, ALK and ROS1 gene rearrangements, and BRAF mutations, with the list of emerging "actionable" targets growing. The 2018 NCCN Guidelines for NSCLC incorporate new therapies, including the EGFR tyrosine kinase inhibitor osimertinib and the ALK inhibitor alectinib, as first-line preferences...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29784046/knockdown-of-annexin-a5-restores-gefitinib-sensitivity-by-promoting-g2-m-cell-cycle-arrest
#11
Jian Zhou, Meijia Chang, Jing Li, Tao Fang, Jie Hu, Chunxue Bai
BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, including gefitinib, are first-line drugs against advanced non-small cell lung cancer with activating EGFR mutations. However, the development of resistance to such drugs is a major clinical challenge. METHODS: The role of annexin A5 in resistance to EGFR tyrosine kinase inhibitors was investigated by qPCR and western blot of relevant molecules, by CCK8 and EdU assay of cell proliferation and viability, by annexin V/propidium iodide assay of apoptosis and cell cycle distribution, by JC-1 assay of mitochondrial integrity, and by xenograft assay of tumorigenicity...
May 21, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29782558/osimertinib-in-untreated-epidermal-growth-factor-receptor-egfr-mutated-advanced-non-small-cell-lung-cancer
#12
EDITORIAL
Vanesa Gregorc, Chiara Lazzari, Niki Karachaliou, Rafael Rosell, Mariacarmela Santarpia
No abstract text is available yet for this article.
April 2018: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/29782359/brca1-mutations-associated-with-increased-risk-of-brain-metastases-in-breast-cancer-a-1-2-matched-pair-analysis
#13
Peter J Zavitsanos, David E Wazer, Jaroslaw T Hepel, Yihong Wang, Kamaljeet Singh, Kara L Leonard
BACKGROUND: Brain metastases (BM) occur in ∼5% of breast cancer patients. BRCA1-associated cancers are often basal-like and basal-like cancers are known to have a predilection for central nervous system metastases. We performed a matched-pair analysis of breast cancer patients with and without BRCA mutations and compared the frequency of BM in both groups. MATERIALS AND METHODS: From a database of 1935 patients treated for localized breast cancer at our institution from 2009 to 2014 we identified 20 patients with BRCA1 or BRCA2 mutations and manually matched 40 patients without BRCA mutations accounting for age, stage, estrogen receptor expression, and human epidermal growth factor receptor 2 (HER2) expression...
May 18, 2018: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29780256/the-utilization-of-next-generation-sequencing-to-detect-somatic-mutations-and-predict-clinical-prognosis-of-chinese-non-small-cell-lung-cancer-patients
#14
Liming Cao, Long Long, Min Li, Huaping Yang, Pengbo Deng, Xinru Mao, Jianxing Xiang, Bing Li, Tengfei Zhang, Chengping Hu
Purpose: The development of next-generation sequencing (NGS) has revolutionized the understanding of oncogenesis of multiple types of cancer, including non-small cell lung cancer (NSCLC). However, there has been some debate over the utility of NGS for predicting patient prognosis and determining molecular targeted therapy. Therefore, we sought to demonstrate the numerous applications of NGS in the prognostic predictions and treatment of NSCLC patients. Materials and methods: We performed NGS on either liquid or tissue tumor biopsies obtained from 53 NSCLC patients...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29776953/the-landscape-of-actionable-genomic-alterations-in-cell-free-circulating-tumor-dna-from-21-807-advanced-cancer-patients
#15
Oliver A Zill, Kimberly C Banks, Stephen R Fairclough, Stefanie Mortimer, James V Vowles, Reza Mokhtari, David R Gandara, Philip C Mack, Justin I Odegaard, Rebecca J Nagy, Arthur M Baca, Helmy Eltoukhy, Darya I Chudova, Richard B Lanman, AmirAli Talasaz
PURPOSE: Cell-free DNA (cfDNA) sequencing provides a non-invasive method for obtaining actionable genomic information to guide personalized cancer treatment, but the presence of multiple alterations in circulation related to treatment and tumor heterogeneity complicate the interpretation of the observed variants. Experimental Design: We describe the somatic mutation landscape of 70 cancer genes from cfDNA deep-sequencing analysis of 21,807 patients with treated, late-stage cancers across >50 cancer types...
May 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29774061/immunotherapy-in-non-metastatic-non-small-cell-lung-cancer-can-the-benefits-of-stage-iv-therapy-be-translated-into-earlier-stages
#16
REVIEW
Griet Deslypere, Dorothée Gullentops, Els Wauters, Johan Vansteenkiste
Over the last decade, several steps forward in the treatment of patients with stage IV non-small cell lung cancer (NCSLC) were made. Examples are the use of pemetrexed, pemetrexed maintenance therapy, or bevacizumab for patients with nonsquamous NSCLC. A big leap forward was the use of tyrosine kinase inhibitors in patients selected on the basis of an activating oncogene, such as epidermal growth factor receptor ( EGFR ) activating mutations or anaplastic lymphoma kinase ( ALK ) translocations. However, all of these achievements could not be translated into survival benefits when studied in randomized controlled trials in patients with nonmetastatic NSCLC...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29769567/genomic-alterations-of-ground-glass-nodular-lung-adenocarcinoma
#17
Hyun Lee, Je-Gun Joung, Hyun-Tae Shin, Duk-Hwan Kim, Yujin Kim, Hojoong Kim, O Jung Kwon, Young Mog Shim, Ho Yun Lee, Kyung Soo Lee, Yoon-La Choi, Woong-Yang Park, D Neil Hayes, Sang-Won Um
In-depth molecular pathogenesis of ground-glass nodular lung adenocarcinoma has not been well understood. The objectives of this study were to identify genomic alterations in ground-glass nodular lung adenocarcinomas and to investigate whether viral transcripts were detected in these tumors. Nine patients with pure (n = 4) and part-solid (n = 5) ground-glass nodular adenocarcinomas were included. Six were females with a median age of 58 years. We performed targeted exon sequencing and RNA sequencing...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29767438/serum-sp70-is-a-sensitive-predictor-of-chemotherapy-response-in-patients-with-advanced-nonsmall-cell-lung-cancer
#18
Jingping Liu, Wei Zhang, Min Gu, Yazhou Ji, Lu Yang, Xiangjun Cheng, Xuelian Xiao, Jian Xu, Chunrong Gu, Jiexin Zhang, Shichang Zhang, Dan Chen, Shiyang Pan
SP70 is a novel tumor biomarker in patients with nonsmall cell lung cancer (NSCLC). However, its role as a marker for predicting the response to chemotherapy for patients with advanced NSCLC has not been investigated. A total of 152 patients were enrolled. Serum SP70, carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and neuron-specific enolase (NSE) were detected before and after 2 cycles of chemotherapy. The correlation between serum tumor biomarker levels and chemotherapy responses and their association with epidermal growth factor receptor (EGFR) mutation status and progression-free survival (PFS) were analyzed...
May 16, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29765556/antibody-assisted-target-identification-reveals-afatinib-an-egfr-covalent-inhibitor-down-regulating-ribonucleotide-reductase
#19
Cheng-Han Yu, Chi-Chi Chou, Hsin-Fang Tu, Wei-Chieh Huang, Ya-Yeh Ho, Kay-Hooi Khoo, Ming-Shyue Lee, Geen-Dong Chang
Afatinib, used for the first-line treatment of non-small-cell lung carcinoma (NSCLC) patients with distinct epidermal growth factor receptor (EGFR) mutations, inactivates EGFR by mimicking ATP structure and forming a covalent adduct with EGFR. We developed a method to unravel potential targets of afatinib in NSCLC cells through immunoprecipitation of afatinib-labeling proteins with anti-afatinib antiserum and mass spectrometry analysis. Ribonucleotide reductase (RNR) is one of target proteins of afatinib revealed by this method...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765525/clinical-characteristics-of-non-small-cell-lung-cancer-harboring-mutations-in-exon-20-of-egfr-or-her2
#20
Masayuki Takeda, Kazuko Sakai, Hidetoshi Hayashi, Kaoru Tanaka, Junko Tanizaki, Takayuki Takahama, Koji Haratani, Kazuto Nishio, Kazuhiko Nakagawa
Unlike common epidermal growth factor receptor gene ( EGFR ) mutations that confer sensitivity to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), mutations in exon 20 of either EGFR or the human EGFR2 gene ( HER2 ) are associated with insensitivity to EGFR-TKIs, with treatment options for patients with such mutations being limited. Clinical characteristics, outcome of EGFR-TKI or nivolumab treatment, and the presence of coexisting mutations were reviewed for NSCLC patients with exon-20 mutations of EGFR or HER2 as detected by routine application of an amplicon-based next-generation sequencing panel...
April 20, 2018: Oncotarget
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