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Lung cancer, breast cancer, mutation, biomarkers

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https://www.readbyqxmd.com/read/29881714/mechanisms-and-therapy-for-cancer-metastasis-to-the-brain
#1
REVIEW
Federica Franchino, Roberta Rudà, Riccardo Soffietti
Advances in chemotherapy and targeted therapies have improved survival in cancer patients with an increase of the incidence of newly diagnosed brain metastases (BMs). Intracranial metastases are symptomatic in 60-70% of patients. Magnetic resonance imaging (MRI) with gadolinium is more sensitive than computed tomography and advanced neuroimaging techniques have been increasingly used in the detection, treatment planning, and follow-up of BM. Apart from the morphological analysis, the most effective tool for characterizing BM is immunohistochemistry...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29718092/updated-results-from-monaleesa-2-a-phase-iii-trial-of-first-line-ribociclib-plus-letrozole-versus-placebo-plus-letrozole-in-hormone-receptor-positive-her2-negative-advanced-breast-cancer
#2
G N Hortobagyi, S M Stemmer, H A Burris, Y S Yap, G S Sonke, S Paluch-Shimon, M Campone, K Petrakova, K L Blackwell, E P Winer, W Janni, S Verma, P Conte, C L Arteaga, D A Cameron, S Mondal, F Su, M Miller, M Elmeliegy, C Germa, J O'Shaughnessy
Background: The phase III MONALEESA-2 study demonstrated significantly prolonged progression-free survival (PFS) and a manageable toxicity profile for first-line ribociclib plus letrozole versus placebo plus letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Here we report updated efficacy and safety data, together with exploratory biomarker analyses, from the MONALEESA-2 study. Patients and methods: A total of 668 postmenopausal women with HR+, HER2- recurrent/metastatic breast cancer were randomized (1:1; stratified by presence/absence of liver and/or lung metastases) to ribociclib (600 mg/day; 3-weeks-on/1-week-off; 28-day treatment cycles) plus letrozole (2...
April 27, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29679564/frequencies-and-expression-levels-of-programmed-death-ligand-1-pd-l1-in-circulating-tumor-rna-ctrna-in-various-cancer-types
#3
Toshiyuki Ishiba, Andreas-Claudius Hoffmann, Joshua Usher, Yahya Elshimali, Todd Sturdevant, Mai Dang, Yolanda Jaimes, Rama Tyagi, Ronald Gonzales, Mary Grino, Jacek K Pinski, Afsaneh Barzi, Luis E Raez, Wilfried E Eberhardt, Dirk Theegarten, Heinz-Josef Lenz, Hiroyuki Uetake, Peter V Danenberg, Kathleen Danenberg
BACKGROUND: Precision medicine and prediction of therapeutic response requires monitoring potential biomarkers before and after treatment. Liquid biopsies provide noninvasive prognostic markers such as circulating tumor DNA and RNA. Circulating tumor RNA (ctRNA) in blood is also used to identify mutations in genes of interest, but additionally, provides information about relative expression levels of important genes. In this study, we analyzed PD-L1 expression in ctRNA isolated from various cancer types...
June 7, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29624369/ultrasensitive-and-facile-detection-of-microrna-via-a-portable-pressure-meter
#4
Lu Shi, Jing Lei, Bei Zhang, Baoxin Li, Chaoyong James Yang, Yan Jin
The upregulation of microRNA (miRNA) is highly related with some kinds of tumor, such as breast, prostate, lung, and pancreatic cancers. Therefore, for an important tumor biomarker, the point-of-care testing (POCT) of miRNA is of significant importance and is in great demand for disease diagnosis and clinical prognoses. Herein, a POCT assay for miRNA detection was developed via a portable pressure meter. Two hairpin DNA probes, H1 and H2, were ingeniously designed and functionalized with magnetic beads (MBs) and platinum nanoparticles (PtNPs), respectively, to form MBs-H1 and PtNPs-H2 complexes...
April 18, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29388903/in-vivo-pet-assay-of-tumor-glutamine-flux-and-metabolism-in-human-trial-of-18-f-2s-4r-4-fluoroglutamine
#5
Mark P S Dunphy, James J Harding, Sriram Venneti, Hanwen Zhang, Eva M Burnazi, Jacqueline Bromberg, Antonio M Omuro, James J Hsieh, Ingo K Mellinghoff, Kevin Staton, Christina Pressl, Bradley J Beattie, Pat B Zanzonico, John F Gerecitano, David P Kelsen, Wolfgang Weber, Serge K Lyashchenko, Hank F Kung, Jason S Lewis
Purpose To assess the clinical safety, pharmacokinetics, and tumor imaging characteristics of fluorine 18-(2S,4R)-4-fluoroglutamine (FGln), a glutamine analog radiologic imaging agent. Materials and Methods This study was approved by the institutional review board and conducted under a U.S. Food and Drug Administration-approved Investigational New Drug application in accordance with the Helsinki Declaration and the Health Insurance Portability and Accountability Act. All patients provided written informed consent...
May 2018: Radiology
https://www.readbyqxmd.com/read/29322935/classifying-cancer-genome-aberrations-by-their-mutually-exclusive-effects-on-transcription
#6
Jonathan B Dayton, Stephen R Piccolo
BACKGROUND: Malignant tumors are typically caused by a conglomeration of genomic aberrations-including point mutations, small insertions, small deletions, and large copy-number variations. In some cases, specific chemotherapies and targeted drug treatments are effective against tumors that harbor certain genomic aberrations. However, predictive aberrations (biomarkers) have not been identified for many tumor types and treatments. One way to address this problem is to examine the downstream, transcriptional effects of genomic aberrations and to identify characteristic patterns...
December 21, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/29124875/emerging-functions-of-the-egfr-in-cancer
#7
REVIEW
Sara Sigismund, Daniele Avanzato, Letizia Lanzetti
The physiological function of the epidermal growth factor receptor (EGFR) is to regulate epithelial tissue development and homeostasis. In pathological settings, mostly in lung and breast cancer and in glioblastoma, the EGFR is a driver of tumorigenesis. Inappropriate activation of the EGFR in cancer mainly results from amplification and point mutations at the genomic locus, but transcriptional upregulation or ligand overproduction due to autocrine/paracrine mechanisms has also been described. Moreover, the EGFR is increasingly recognized as a biomarker of resistance in tumors, as its amplification or secondary mutations have been found to arise under drug pressure...
January 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29061138/the-evidence-base-for-circulating-tumour-dna-blood-based-biomarkers-for-the-early-detection-of-cancer-a-systematic-mapping-review
#8
Ian A Cree, Lesley Uttley, Helen Buckley Woods, Hugh Kikuchi, Anne Reiman, Susan Harnan, Becky L Whiteman, Sian Taylor Philips, Michael Messenger, Angela Cox, Dawn Teare, Orla Sheils, Jacqui Shaw
BACKGROUND: The presence of circulating cell-free DNA from tumours in blood (ctDNA) is of major importance to those interested in early cancer detection, as well as to those wishing to monitor tumour progression or diagnose the presence of activating mutations to guide treatment. In 2014, the UK Early Cancer Detection Consortium undertook a systematic mapping review of the literature to identify blood-based biomarkers with potential for the development of a non-invasive blood test for cancer screening, and which identified this as a major area of interest...
October 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28451462/pulmonary-adenocarcinoma-with-mucin-production-modulates-phenotype-according-to-common-genetic-traits-a-reappraisal-of-mucinous-adenocarcinoma-and-colloid-adenocarcinoma
#9
Angelica Sonzogni, Fabrizio Bianchi, Alessandra Fabbri, Mara Cossa, Giulio Rossi, Alberto Cavazza, Elena Tamborini, Federica Perrone, Adele Busico, Iolanda Capone, Benedetta Picciani, Barbara Valeri, Ugo Pastorino, Giuseppe Pelosi
Whether invasive mucinous adenocarcinoma (IMA) and colloid adenocarcinoma (ICA) of the lung represent separate tumour entities, or simply lie within a spectrum of phenotypic variability, is worth investigating. Fifteen ICA, 12 IMA, 9 ALK-rearranged adenocarcinomas (ALKA), 8 non-mucinous KRAS-mutated adenocarcinomas (KRASA) and 9 mucinous breast adenocarcinomas (MBA) were assessed by immunohistochemistry for alveolar (TTF1, cytoplasmic MUC1), intestinal (CDX-2, MUC2), gastric (membrane MUC1, MUC6), bronchial (MUC5AC), mesenchymal (vimentin), neuroendocrine (chromogranin A, synaptophysin), sex steroid hormone-related (oestrogen and progesterone receptors), pan-mucinous (HNF4A) and pan-epithelial (keratin 7) lineage biomarkers and by targeted next generation sequencing (TNGS) for 50 recurrently altered cancer genes...
April 2017: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/28212573/dynamic-variations-in-epithelial-to-mesenchymal-transition-emt-atm-and-slfn11-govern-response-to-parp-inhibitors-and-cisplatin-in-small-cell-lung-cancer
#10
C Allison Stewart, Pan Tong, Robert J Cardnell, Triparna Sen, Lerong Li, Carl M Gay, Fatemah Masrorpour, You Fan, Rasha O Bara, Ying Feng, Yuanbin Ru, Junya Fujimoto, Samrat T Kundu, Leonard E Post, Karen Yu, Yuqiao Shen, Bonnie S Glisson, Ignacio Wistuba, John V Heymach, Don L Gibbons, Jing Wang, Lauren Averett Byers
Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/27833666/the-role-of-testosterone-in-colorectal-carcinoma-pathomechanisms-and-open-questions
#11
REVIEW
Mohsin H K Roshan, Amos Tambo, Nikolai P Pace
Colorectal cancer (CRC) is the fourth commonest type of malignancy after breast, lung and prostate in the USA and accounts for approximately 49,190 deaths annually in USA alone. The 5-year survival rate of CRC has increased over the past decades, in part, due to greater awareness and the widespread implementation of national screening programmes. Recently, a number of studies reported that males have a higher risk of developing CRC due to the action of testosterone. Testosterone is an androgen that is responsible for the development of male secondary sex characteristics and for spermatogenesis...
2016: EPMA Journal
https://www.readbyqxmd.com/read/27744717/the-prospect-of-patritumab-for-treating-non-small-cell-lung-cancer
#12
REVIEW
Hidehito Horinouchi
The mutation or expression of HER family members serves as a therapeutic target for tyrosine kinase inhibitors or monoclonal antibodies in diverse cancers, such as non-small cell lung cancer, breast cancer, gastric cancer, head and neck cancer, colorectal cancer, pancreatic cancer and glioblastoma. HER3, which heterodimerizes with HER1 and HER2, has received much attention as a potential target for anti-EGFR treatment. Patritumab is a novel, fully human monoclonal antibody directed against HER3. Areas covered: In this review article, an overview of the market, chemistry, pharmacodynamics, pharmacokinetics, efficacy, and safety of patritumab is provided based on data from phase I studies, a combination phase I trial, and a randomized phase II trial comparing two doses of patritumab...
December 2016: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/27250969/therapeutic-potential-of-taxanes-in-the-treatment-of-metastatic-pancreatic-cancer
#13
REVIEW
Radmila Lemstrova, Bohuslav Melichar, Beatrice Mohelnikova-Duchonova
Most patients with pancreatic ductal adenocarcinoma (PDAC) present with unresectable or metastatic disease with very poor prognosis. Chemotherapy is the primary treatment modality for patients with locally advanced and metastatic PDAC, but the efficacy of currently available regimens is limited. Taxanes are widely used in many primary cancers including breast, ovarian and lung cancers. The activity of combined regimen of taxanes plus nucleoside analogue or platinum derivate in terms of response rate ranges between 20 and 57 % in PDAC and may prolong overall survival...
December 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27029813/multivariate-models-from-rna-seq-snvs-yield-candidate-molecular-targets-for-biomarker-discovery-snv-da
#14
Matt R Paul, Nicholas P Levitt, David E Moore, Patricia M Watson, Robert C Wilson, Chadrick E Denlinger, Dennis K Watson, Paul E Anderson
BACKGROUND: It has recently been shown that significant and accurate single nucleotide variants (SNVs) can be reliably called from RNA-Seq data. These may provide another source of features for multivariate predictive modeling of disease phenotype for the prioritization of candidate biomarkers. The continuous nature of SNV allele fraction features allows the concurrent investigation of several genomic phenomena, including allele specific expression, clonal expansion and/or deletion, and copy number variation...
March 31, 2016: BMC Genomics
https://www.readbyqxmd.com/read/26634009/epigenetic-inactivation-of-the-extracellular-matrix-metallopeptidase-adamts19-gene-and-the-metastatic-spread-in-colorectal-cancer
#15
Sergio Alonso, Beatriz González, Tatiana Ruiz-Larroya, Mercedes Durán Domínguez, Takaharu Kato, Akihiro Matsunaga, Koichi Suzuki, Alex Y Strongin, Pepita Gimènez-Bonafé, Manuel Perucho
BACKGROUND: ADAMTS19 encodes a member of the ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin motifs) protein family with emerging roles in carcinogenesis and metastasis. ADAMTS shares several distinct protein modules including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. In a previous work, we found ADAMTS19 frequently hypermethylated in colorectal cancer (CRC). We explored the association of methylation with tumor genotype and phenotype...
2015: Clinical Epigenetics
https://www.readbyqxmd.com/read/26623053/mutational-analysis-of-the-insulin-like-growth-factor-1-receptor-tyrosine-kinase-domain-in-non-small-cell-lung-cancer-patients
#16
Kathy Gately, Lydia Forde, Stephen Gray, Derek Morris, Aidan Corvin, Prerna Tewari, Kenneth O'Byrne
The insulin-like growth factor 1 receptor (IGF1R) pathway plays an important role in the pathogenesis of non-small cell lung cancer (NSCLC) and also provides a mechanism of resistance to targeted therapies. IGF1R is therefore an ideal therapeutic target and several inhibitors have entered clinical trials. However, thus far the response to these inhibitors has been poor, highlighting the importance of predictive biomarkers to identify patient cohorts who will benefit from these targeted agents. It is well-documented that mutations and/or deletions in the epidermal growth factor receptor (EGFR) tyrosine kinase (TK) domain predict sensitivity of NSCLC patients to EGFR TK inhibitors...
September 2015: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/26588676/tumor-infiltrating-lymphocyte-therapy-addressing-prevailing-questions
#17
REVIEW
Laszlo G Radvanyi
Autologous adoptive T-cell therapies have made tremendous strides over the last few years with excitement currently being generated by technologies that can reprogram T-cell specificities toward any desired antigen including chimeric antigen receptors and recombinant T-cell receptors. Time will tell whether these new genetically engineered T-cell technologies will be effective as advertised, especially in solid tumors, considering the limited availability of specific antigens and the difficulty in managing the unpredictable on-target, off-tissue toxicities...
November 2015: Cancer Journal
https://www.readbyqxmd.com/read/26580964/met-gene-amplification-and-met-receptor-activation-are-not-sufficient-to-predict-efficacy-of-combined-met-and-egfr-inhibitors-in-egfr-tki-resistant-nsclc-cells
#18
Dario Presutti, Simonetta Santini, Beatrice Cardinali, Giuliana Papoff, Cristiana Lalli, Simone Samperna, Valentina Fustaino, Giuseppe Giannini, Giovina Ruberti
Epidermal growth factor receptor (EGFR), member of the human epidermal growth factor receptor (HER) family, plays a critical role in regulating multiple cellular processes including proliferation, differentiation, cell migration and cell survival. Deregulation of the EGFR signaling has been found to be associated with the development of a variety of human malignancies including lung, breast, and ovarian cancers, making inhibition of EGFR the most promising molecular targeted therapy developed in the past decade against cancer...
2015: PloS One
https://www.readbyqxmd.com/read/26516350/integration-and-comparison-of-different-genomic-data-for-outcome-prediction-in-cancer
#19
Hugo Gómez-Rueda, Emmanuel Martínez-Ledesma, Antonio Martínez-Torteya, Rebeca Palacios-Corona, Victor Trevino
BACKGROUND: In cancer, large-scale technologies such as next-generation sequencing and microarrays have produced a wide number of genomic features such as DNA copy number alterations (CNA), mRNA expression (EXPR), microRNA expression (MIRNA), and DNA somatic mutations (MUT), among others. Several analyses of a specific type of these genomic data have generated many prognostic biomarkers in cancer. However, it is uncertain which of these data is more powerful and whether the best data-type is cancer-type dependent...
2015: BioData Mining
https://www.readbyqxmd.com/read/26373821/the-importance-of-molecular-markers-for-diagnosis-and-selection-of-targeted-treatments-in-patients-with-cancer
#20
REVIEW
N P Tobin, T Foukakis, L De Petris, J Bergh
The past 30 years have seen the introduction of a number of cancer therapies with the aim of restricting the growth and spread of primary and metastatic tumours. A shared commonality among these therapies is their targeting of various aspects of the cancer hallmarks, that is traits that are essential to successful tumour propagation and dissemination. The evolution of molecular-scale technology has been central to the identification of new cancer targets, and it is not a coincidence that improved therapies have emerged at the same time as gene expression arrays and DNA sequencing have enhanced our understanding of cancer genetics...
December 2015: Journal of Internal Medicine
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