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https://www.readbyqxmd.com/read/28231414/mir-135a-3p-as-a-promising-biomarker-and-nucleic-acid-therapeutic-agent-for-ovarian-cancer
#1
Satoshi Fukagawa, Kohei Miyata, Fusanori Yotsumoto, Chihiro Kiyoshima, Sung Ouk Nam, Haruchika Anan, Takahiro Katsuda, Daisuke Miyahara, Masaharu Murata, Hiroshi Yagi, Kyoko Shirota, Shin'ichiro Yasunaga, Kiyoko Kato, Shingo Miyamoto
Ovarian cancer is the most lethal gynecologic malignancy. Recently, several molecularly targeted anticancer agents have been developed for ovarian cancer; however, its prognosis has remained extremely poor. The development of molecularly targeted therapy, as well as companion diagnostics, is required to improve outcomes for patients with ovarian cancer. In this study, to identify microRNAs involved in the progression of ovarian cancer we analyzed serum microRNAs in patients with ovarian cancer using microRNA array and qRT-PCR and examined the anticancer properties of microRNA expression in ovarian cancer cells...
February 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/28230858/ngs-based-transcriptome-profiling-reveals-biomarkers-for-companion-diagnostics-of-the-tgf-%C3%AE-receptor-blocker-galunisertib-in-hcc
#2
Yuan Cao, Rahul Agarwal, Francesco Dituri, Luigi Lupo, Paolo Trerotoli, Serena Mancarella, Peter Winter, Gianluigi Giannelli
Transforming growth factor-beta (TGF-β) signaling has gained extensive interest in hepatocellular carcinoma (HCC). The small molecule kinase inhibitor galunisertib, targeting the TGF-β receptor I (TGF-βRI), blocks HCC progression in preclinical models and shows promising effects in ongoing clinical trials. As the drug is not similarly effective in all patients, this study was aimed at identifying new companion diagnostics biomarkers for patient stratification. Next-generation sequencing-based massive analysis of cDNA ends was used to investigate the transcriptome of an invasive HCC cell line responses to TGF-β1 and galunisertib...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28214087/targeting-the-pd-1-pd-l1-axis-in-non-small-cell-lung-cancer
#3
REVIEW
Rajiv Kumar, Dearbhaile Collins, Saoirse Dolly, Fiona McDonald, Mary E R O'Brien, Timothy A Yap
The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics have led to the registration of multiple PD-1 and PD-L1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, in second-line advanced NSCLC, whereas durvalumab and avelumab are in late-phase clinical testing...
December 23, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28183714/dichotomous-alk-ihc-is-a-better-predictor-for-alk-inhibition-outcome-than-traditional-alk-fish-in-advanced-non-small-cell-lung-cancer
#4
Anthonie van der Wekken, Rianne Pelgrim, Nils 't Hart, Naomi Werner, Mirjam Mastik, Lizza Hendriks, Erik Hfm van der Heijden, Monika Looijen-Salamon, A Joop de Langen, Jeske Staal-van den Brekel, Sietske Riemersma, Ben E van den Borne, Ernst-Jan M Speel, Anne-Marie C Dingemans, T Jeroen N Hiltermann, Anke van den Berg, Wim Timens, Ed Schuuring, Harry Jm Groen
ALK rearrangement detection using fluorescence in situ hybridization (FISH) is the standard test to identify non-small cell lung carcinoma (NSCLC) patients eligible for treatment with ALK inhibitors. Recently ALK protein expression in resectable NSCLC showed predictive value. We evaluated tumor response rate and survival after crizotinib treatment of advanced NSCLC patients with ALK activation using both dichotomous immunohistochemical staining (IHC) and FISH. Design Stage IV NSCLC patients treated with crizotinib were selected...
February 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28161563/single-center-experience-with-a-targeted-next-generation-sequencing-assay-for-assessment-of-relevant-somatic-alterations-in-solid-tumors
#5
Aino Paasinen-Sohns, Viktor H Koelzer, Angela Frank, Julian Schafroth, Aline Gisler, Melanie Sachs, Anne Graber, Sacha I Rothschild, Andreas Wicki, Gieri Cathomas, Kirsten D Mertz
Companion diagnostics rely on genomic testing of molecular alterations to enable effective cancer treatment. Here we report the clinical application and validation of the Oncomine Focus Assay (OFA), an integrated, commercially available next-generation sequencing (NGS) assay for the rapid and simultaneous detection of single nucleotide variants, short insertions and deletions, copy number variations, and gene rearrangements in 52 cancer genes with therapeutic relevance. Two independent patient cohorts were investigated to define the workflow, turnaround times, feasibility, and reliability of OFA targeted sequencing in clinical application and using archival material...
February 2, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28159919/evaluation-of-radiofluorinated-carboximidamides-as-potential-ido-targeted-pet-tracers-for-cancer-imaging
#6
Xuan Huang, Zhongjie Pan, Michael L Doligalski, Xia Xiao, Epifanio Ruiz, Mikalai M Budzevich, Haibin Tian
IDO1 is an enzyme catalyzing the initial and rate-limiting step in the catabolism of tryptophan along the kynurenine pathway. IDO1 expression could suppress immune responses by blocking T-lymphocyte proliferation locally, suggesting a role of IDO in the regulation of immune responses. The goal of this study was to evaluate the potential of radiofluorinated carboximidamides as selective PET radioligands for IDO1. Specific binding correlated with IDO1 expression as measured through in vitro, microPET experiments...
January 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28157707/near-infrared-fluorescent-imaging-of-choline-kinase-alpha-expression-and-inhibition-in-breast-tumors
#7
Sean P Arlauckas, Manoj Kumar, Anatoliy V Popov, Harish Poptani, Edward J Delikatny
Choline kinase alpha (ChoKα) overexpression is associated with an aggressive tumor phenotype. ChoKα inhibitors induce apoptosis in tumors, however validation of their specificity is difficult in vivo. We report the use of optical imaging to assess ChoKα status in cells and in vivo using JAS239, a carbocyanine-based ChoKα inhibitor with inherent near infrared fluorescence. JAS239 attenuated choline phosphorylation and viability in a panel of human breast cancer cell lines. Antibody blockade prevented cellular retention of JAS239 indicating direct interaction with ChoKα independent of the choline transporters and catabolic choline pathways...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28149844/companion-diagnostics-a-tool-to-improve-pharmacotherapy
#8
REVIEW
Jan Trøst Jørgensen, Maria Hersom
The variability of pharmacotherapy can be of a significant magnitude, and the main reason for this is often diseases heterogeneity. Patients who have similar diagnoses very often respond differently to the same pharmacological intervention, with great variability in both efficacy and safety outcome. Despite having discussed personalized medicine for more than a decade, we still see that most drug prescriptions for severe chronic diseases are largely based on 'trial and error' and not on solid biomarker data...
December 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28147239/a-sensitive-alk-immunohistochemistry-companion-diagnostic-test-identifies-patients-eligible-for-treatment-with-crizotinib
#9
Trish Thorne-Nuzzo, Crystal Williams, Alice Catallini, June Clements, Shalini Singh, James Amberson, Kim Dickinson, Zoran Gatalica, Steffan N Ho, Isabell Loftin, Abigail McElhinny, Penny Towne
INTRODUCTION: The availability of high quality, rigorously validated diagnostic tests that can be broadly implemented is necessary to efficiently identify patients with anaplastic lymphoma kinase (ALK) NSCLC who can potentially benefit from treatment with crizotinib. Here we present data on the recently approved VENTANA ALK (D5F3) CDx Assay (ALK (D5F3) CDx), the only immunohistochemistry (IHC) based assay linked to treatment outcome. METHODS: NSCLC specimens prospectively tested for ALK status by Flourescent In-situ Hybridization (FISH) in the PROFILE 1014 clinical trial of crizotinib versus chemotherapy (N=1018, including 179 ALK(+) and 754 ALK(-) specimens), were evaluated using the ALK (D5F3) CDx assay...
January 29, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28119429/novel-assay-to-detect-rna-polymerase-i-activity-in-vivo
#10
Gunes Guner, Paul Sirajuddin, Qizhi Zheng, Baoyan Bai, Alexandra Brodie, Hester Liu, Taija Af Hallstrom, Ibrahim Kulac, Marikki Laiho, Angelo M De Marzo
: This report develops an analytically validated chromogenic in situ hybridization (CISH) assay using branched DNA signal amplification (RNAscope) for detecting the expression of the 5' external transcribed spacer (ETS) of the 45S ribosomal (r) RNA precursor in formalin fixed and paraffin embedded (FFPE) human tissues. 5'ETS/45S CISH was performed on standard clinical specimens and tissue microarrays (TMAs) from untreated prostate carcinomas, high-grade prostatic intraepithelial neoplasia (PIN) and matched benign prostatic tissues...
January 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28118758/molecular-classification-of-gastric-cancer
#11
Christoph Röcken
Gastric cancer is among the most common cancers worldwide. Despite declining incidences, the prognosis remains dismal in Western countries and is better in Asian countries with national cancer screening programs. Complete endoscopic or surgical resection of the primary tumor with or without lymphadenectomy offers the only chance of cure in the early stage of the disease. Survival of more locally advanced gastric cancers was improved by the introduction of perioperative, adjuvant and palliative chemotherapy...
March 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28078645/parp-inhibitors-in-reproductive-system-cancers-current-use-and-developments
#12
REVIEW
Geraldine O'Sullivan Coyne, Alice P Chen, Robert Meehan, James H Doroshow
The repair of DNA damage is a critical cellular process governed by multiple biochemical pathways that are often found to be defective in cancer cells. The poly(ADP-ribose) polymerase (PARP) family of proteins controls response to single-strand DNA breaks by detecting these damaged sites and recruiting the proper factors for repair. Blocking this pathway forces cells to utilize complementary mechanisms to repair DNA damage. While PARP inhibition may not, in itself, be sufficient to cause tumor cell death, inhibition of DNA repair with PARP inhibitors is an effective cytotoxic strategy when it is used in patients who carry other defective DNA-repair mechanisms, such as mutations in the genes BRCA 1 and 2...
February 2017: Drugs
https://www.readbyqxmd.com/read/28077296/extracellular-vesicle-communication-pathways-as-regulatory-targets-of-oncogenic-transformation
#13
REVIEW
Dongsic Choi, Tae Hoon Lee, Cristiana Spinelli, Shilpa Chennakrishnaiah, Esterina D'Asti, Janusz Rak
Pathogenesis of human cancers bridges intracellular oncogenic driver events and their impact on intercellular communication. Among multiple mediators of this 'pathological connectivity' the role of extracellular vesicles (EVs) and their subsets (exosomes, ectosomes, oncosomes) is of particular interest for several reasons. The release of EVs from cancer cells represents a unique mechanism of regulated expulsion of bioactive molecules, a process that also mediates cell-to-cell transfer of lipids, proteins, and nucleic acids...
January 8, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28060367/applications-of-molecular-testing-in-surgical-pathology-of-the-head-and-neck
#14
Jennifer L Hunt
Molecular testing in routine surgical pathology is becoming an important component of the workup of many different types of tumors. In fact, in some organ systems, guidelines now suggest that the standard of care is to obtain specific molecular panels for tumor classification and/or therapeutic planning. In the head and neck, clinically applicable molecular tests are not as abundant as in other organ systems. Most current head and neck biomarkers are utilized for diagnosis rather than as companion diagnostic tests to predict therapeutic response...
January 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28057616/rucaparib-approved-for-ovarian-cancer
#15
(no author information available yet)
The FDA approved the PARP inhibitor rucaparib to treat women with advanced ovarian cancer who have already been treated with at least two chemotherapies and have a BRCA1 or BRCA2 gene mutation identified by an approved companion diagnostic test. The agency also gave a nod to the FoundationFocus CDxBRCA test to detect BRCA alterations.
January 5, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28044295/negative-enrichment-of-circulating-tumor-cells-in-blood-using-a-microfluidic-chip
#16
Hamizah A Cognart, Chia-Pin Chang
The enumeration and analysis of circulating tumor cells (CTCs) is an increasing interest for monitoring disease progression or response to treatment, specifically as a companion diagnostic for new anticancer drugs, and for research into the mechanisms of disease progression and metastases. Ideally, CTCs would be enriched from very small samples, with minimal handling, high recovery, and no requirement for the expression of specific surface markers. Here, we describe negative enrichment as the preferred approach for cancer cell isolation using a microfluidic platform...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28032602/detection-of-alk-rearrangements-in-lung-cancer-patients-using-a-homebrew-pcr-assay
#17
Hui Yu, JianHua Chang, Fang Liu, Qifeng Wang, YongMing Lu, ZhuanXu Zhang, Jiabing Shen, Qing Zhai, Xia Meng, Jialei Wang, Xun Ye
Lung cancer patients with anaplastic lymphoma kinase (ALK) rearrangements are candidates for targeted therapeutics. However, patients must be tested with a companion diagnostic assay to realize their ALK rearrangement status. We analyzed the publicly available E-GEOD-31210 microarray dataset and identified a non-coding RNA, sweyjawbu, which is strongly associated with ALK rearrangements. We validated these results using quantitative real-time PCR in an independent cohort consisting of 4 cell lines and 83 clinical samples...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28000172/implementation-of-a-precision-pathology-program-focused-on-oncology-based-prognostic-and-predictive-outcomes
#18
Michael J Donovan, Carlos Cordon-Cardo
Personalized or precision medicine as a diagnostic and therapeutic paradigm was introduced some 10-15 years ago, with the advent of biomarker discovery as a mechanism for identifying prognostic and predictive attributes associated with treatment indication and outcome. While the concept is not new, the successful development and implementation of novel 'companion diagnostics', especially in oncology, continues to represent a significant challenge and is currently at the forefront of smart trial design and therapeutic choice...
December 20, 2016: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/27993967/an-fda-perspective-on-the-regulatory-implications-of-complex-signatures-to-predict-response-to-targeted-therapies
#19
Julia A Beaver, Abraham Tzou, Gideon M Blumenthal, Amy E McKee, Geoffrey Kim, Richard Pazdur, Reena Philip
As technologies evolve, and diagnostics move from detection of single biomarkers toward complex signatures, an increase in the clinical use and regulatory submission of complex signatures is anticipated. However, to date, no complex signatures have been approved as companion diagnostics. In this article, we will describe the potential benefit of complex signatures and their unique regulatory challenges including analytical performance validation, complex signature simulation, and clinical performance evaluation...
December 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27993328/diagnostic-quality-assurance-pilot-a-model-to-demonstrate-comparative-laboratory-test-performance-with-an-oncology-companion-diagnostic-assay
#20
EDITORIAL
Barbara Zehnbauer, Catherine Lofton-Day, John Pfeifer, Elizabeth Shaughnessy, Lindee Goh
This Editorial highlights a model demonstrating laboratory test performance with a companion diagnostic assay.
January 2017: Journal of Molecular Diagnostics: JMD
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