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pancreatic cancer molecular classification

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https://www.readbyqxmd.com/read/29771769/systemic-chemotherapy-for-advanced-rare-pancreatic-histotype-tumors-a-retrospective-multicenter-analysis
#1
Oronzo Brunetti, Giuseppe Aprile, Paolo Marchetti, Enrico Vasile, Andrea Casadei Gardini, Mario Scartozzi, Sandro Barni, Sara Delfanti, Fernando De Vita, Francesco Di Costanzo, Michele Milella, Chiara Alessandra Cella, Rossana Berardi, Ivana Cataldo, Aldo Scarpa, Debora Basile, Federica Mazzuca, Giusi Graziano, Antonella Argentiero, Daniele Santini, Michele Reni, Stefano Cascinu, Nicola Silvestris
OBJECTIVES: Two issues were put forth by clinicians in the management of the advanced stages of rare variants of pancreatic ductal adenocarcinoma and other exocrine histotypes with peculiar clinical and pathological features: Do chemotherapy regimens recommended in pancreatic ductal adenocarcinoma patients have a clinical activity in rare pancreatic tumors? Or should other chemotherapy combinations be considered in this subset of patients? METHODS: We conducted a multicenter retrospective study that collected data from 2005 to 2016 at 14 Italian cancer centers with the aim to evaluate tumor response and time to progression for first- and second-line and overall survival...
May 15, 2018: Pancreas
https://www.readbyqxmd.com/read/29661773/integrated-genomic-and-immunophenotypic-classification-of-pancreatic-cancer-reveals-three-distinct-subtypes-with-prognostic-predictive-significance
#2
Martin Wartenberg, Silvia Cibin, Inti Zlobec, Erik Vassella, Serenella M M Eppenberger-Castori, Luigi Terracciano, Micha Eichmann, Mathias Worni, Beat Gloor, Aurel Perren, Eva Karamitopoulou
PURPOSE: Current clinical classification of pancreatic ductal adenocarcinoma (PDAC) is unable to predict prognosis or response to chemo- or immunotherapy and does not take into account the host reaction to PDAC-cells. Our aim is to classify PDAC according to host- and tumor-related factors into clinically/biologically relevant subtypes by integrating molecular and microenvironmental findings. EXPERIMENTAL DESIGN: A well-characterized PDAC-cohort (n=110) underwent next-generation sequencing with a hotspot cancer panel, while Next-generation Tissue-Microarrays were immunostained for CD3, CD4, CD8, CD20, PD-L1, p63, hyaluronan-mediated motility receptor (RHAMM) and DNA mismatch-repair proteins...
April 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29537309/pancreatic-cancer-subtypes-a-roadmap-for-precision-medicine
#3
Carolina Torres, Paul J Grippo
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cause of cancer-related deaths by 2020. Although it has traditionally been approached as a disease, accumulated evidences point to the clinical heterogeneity of this disease, which translate into disparity in outcomes among the patients. Much emphasis has been put into patient classification introducing a platform for more tailored therapies. In the last 10 years, there have been important advances in the understanding of the molecular pathogenesis of PDAC, which has culminated with a comprehensive integrated genomic analysis from RNA expression profiles...
June 2018: Annals of Medicine
https://www.readbyqxmd.com/read/29499330/molecular-classification-as-prognostic-factor-and-guide-for-treatment-decision-of-pancreatic-cancer
#4
REVIEW
David J Birnbaum, François Bertucci, Pascal Finetti, Daniel Birnbaum, Emilie Mamessier
Clinico-pathological factors fail to consistently predict the outcome after pancreatic resection for pancreatic ductal adenocarcinoma (PDAC). PDACs show a high level of inter- and intra- tumor genetic heterogeneity. A molecular classification should help sort patients into less heterogeneous and more appropriate groups regarding the metastatic risk and the therapeutic response, with the consequences of better predicting evolution and better orienting the treatment. PDAC can be classified based on mutational subtypes and 18gene alterations...
April 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29382042/extracellular-influences-molecular-subclasses-and-the-microenvironment-in-pancreatic-cancer
#5
REVIEW
Veronique L Veenstra, Andrea Garcia-Garijo, Hanneke W van Laarhoven, Maarten F Bijlsma
Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent form of pancreatic cancer and carries the worst prognosis of all common cancers. Five-year survival rates have not surpassed 6% for some decades and this lack of improvement in outcome urges a better understanding of the PDAC-specific features which contribute to this poor result. One of the most defining features of PDAC known to contribute to its progression is the abundance of non-tumor cells and material collectively known as the stroma. It is now well recognized that the different non-cancer cell types, signalling molecules, and mechanical properties within a tumor can have both tumor-promoting as well as -inhibitory effects...
January 27, 2018: Cancers
https://www.readbyqxmd.com/read/29296236/combined-microrna-and-mrna-microfluidic-taqman-array-cards-for-the-diagnosis-of-malignancy-of-multiple-types-of-pancreatico-biliary-tumors-in-fine-needle-aspiration-material
#6
Thomas M Gress, Ludwig Lausser, Lyn-Rouven Schirra, Lisa Ortmüller, Ramona Diels, Bo Kong, Christoph W Michalski, Thilo Hackert, Oliver Strobel, Nathalia A Giese, Miriam Schenk, Rita T Lawlor, Aldo Scarpa, Hans A Kestler, Malte Buchholz
Pancreatic ductal adenocarcinoma (PDAC) continues to carry the lowest survival rates among all solid tumors. A marked resistance against available therapies, late clinical presentation and insufficient means for early diagnosis contribute to the dismal prognosis. Novel biomarkers are thus required to aid treatment decisions and improve patient outcomes. We describe here a multi-omics molecular platform that allows for the first time to simultaneously analyze miRNA and mRNA expression patterns from minimal amounts of biopsy material on a single microfluidic TaqMan Array card...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29273547/-molecular-characterisation-defines-several-subtypes-of-pancreatic-ductal-adenocarcinoma
#7
REVIEW
Jérôme Raffenne, Jérôme Cros
Multi-omics high throughput analyses lead to the description of multiple molecular subtypes of pancreatic adenocarcinoma with major prognostic impact for most of them. There is no consensual multilevel integrative classification yet like in colon or breast cancers. Genomic classifications have identified a tumor subtype (15% of the patients) with deficient homologous DNA repair-system leading to increase sensitivity to platinum-based therapies and possibly to PARP inhibitors and immunotherapies. Transcriptomic classifications are still debated but all have identified an aggressive subtype with a very poor prognosis, presumably unfit for a surgical approach...
January 2018: Bulletin du Cancer
https://www.readbyqxmd.com/read/29102946/circulating-tumor-cells-as-an-auxiliary-diagnostic-tool-in-surgery
#8
Katarina Kolostova, Adam Rzechonek, Jan Schützner, Robert Grill, Robert Lischke, Pavel Hladik, Jan Simonek, Vladimir Bobek
BACKGROUND: In general, the presence of circulating tumor cells (CTCs) in peripheral blood (PB) is associated with a relative shorter overall survival in cancer patients. The clinical utility of CTC diagnostics is changing: from prognostic test to an assay predicting therapy response, enabling the right choice of therapy and monitoring the effect of administered therapy. We present two case reports of patients with suspicion of lung and pancreatic cancer, without obtainable preoperative biopsy for histological verification...
November 2017: In Vivo
https://www.readbyqxmd.com/read/28736626/molecular-landscape-and-sub-classification-of-gastrointestinal-cancers-a-review-of-literature
#9
REVIEW
Bita Fakhri, Kian-Huat Lim
The historical approach of diagnosing cancer types based entirely on anatomic origin and histologic features, and the "one-size-fit-all" therapeutic approach, are inadequate in modern cancer treatment. From decades of research we now know that cancer is a highly heterogeneous disease driven by complex genetic or epigenetic alterations. The advent of various high throughput molecular tools has now enabled us to view and sub-classify each cancer type based on their distinct molecular features, in addition to histologic classification, with the promise of individualized treatment strategies tailored towards each specific subtype to improve patient outcomes...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28723307/nationwide-comprehensive-gastro-intestinal-cancer-cohorts-the-3p-initiative
#10
R R J Coebergh van den Braak, L B van Rijssen, J J van Kleef, G R Vink, M Berbee, M I van Berge Henegouwen, H J Bloemendal, M J Bruno, M C Burgmans, O R C Busch, P P L O Coene, V M H Coupé, J W T Dekker, C H J van Eijck, M A G Elferink, F L G Erdkamp, W M U van Grevenstein, J W B de Groot, N C T van Grieken, I H J T de Hingh, M C C M Hulshof, J N M Ijzermans, L Kwakkenbos, V E P P Lemmens, M Los, G A Meijer, I Q Molenaar, G A P Nieuwenhuijzen, M E de Noo, L V van de Poll-Franse, C J A Punt, R C Rietbroek, W W H Roeloffzen, T Rozema, J P Ruurda, J W van Sandick, A H W Schiphorst, H Schipper, P D Siersema, M Slingerland, D W Sommeijer, M C W Spaander, M A G Sprangers, H B A C Stockmann, M Strijker, G van Tienhoven, L M Timmermans, M L R Tjin-A-Ton, A M T van der Velden, M J Verhaar, H M Verkooijen, W J Vles, J M P G M de Vos-Geelen, J W Wilmink, D D E Zimmerman, M G H van Oijen, M Koopman, M G H Besselink, H W M van Laarhoven
BACKGROUND: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients...
February 2018: Acta Oncologica
https://www.readbyqxmd.com/read/28611293/identification-of-molecular-biomarkers-for-pancreatic-cancer-with-mrmr-shortest-path-method
#11
Shuhua Shen, Tuantuan Gui, Chengcheng Ma
The high mortality rate of pancreatic cancer makes it one of the most studied diseases among all cancer types. Many researches have been conducted to understand the mechanism underlying its emergence and pathogenesis of this disease. Here, by using minimum-redundancy-maximum-relevance (mRMR) method, we studied a set of transcriptome data of pancreatic cancer. As we gradually added features to achieve the most accurate classification results of Jackknife, a gene set of 9 genes was identified. They were NHS, SCML2, LAMC2, S100P, COL17A1, AMIGO2, PTPRR, KPNA7 and KCNN4...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400627/molecular-subtypes-in-cancers-of-the-gastrointestinal-tract
#12
REVIEW
Maarten F Bijlsma, Anguraj Sadanandam, Patrick Tan, Louis Vermeulen
Malignancies of the gastrointestinal tract are among the most common human cancers. The distinct tissues of origin give rise to a diverse set of diseases, such as colorectal cancer, pancreatic carcinoma and gastric cancers, with each associating with specific clinical features. Genomic and transcriptomic analyses have further defined the heterogeneity that occurs within these cancers by identifying so-called molecular subtypes. These subtypes are characterized by specific genetic aberrations and expression signatures that suggest important biological differences...
June 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28367231/molecular-subtyping-of-pancreatic-cancer-translating-genomics-and-transcriptomics-into-the-clinic
#13
REVIEW
Yongxing Du, Bangbo Zhao, Ziwen Liu, Xiaoxia Ren, Wenjing Zhao, Zongze Li, Lei You, Yupei Zhao
Pancreatic cancer remains one of the most lethal malignancies, and insights into both personalized diagnosis and intervention of this disease are urgently needed. The rapid development of sequencing technologies has enabled the successive completion of a series of genetic and epigenetic sequencing studies of pancreatic cancer. The mutational landscape of pancreatic cancer is generally portrayed in terms of somatic mutations, structural variations, epigenetic alterations and the core signaling pathways. In recent years, four significant molecular subtype classifications of pancreatic cancer have been proposed based on the expression of transcription factors and downstream targets or the distribution of structural rearrangements...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28283209/predicting-novel-salivary-biomarkers-for-the-detection-of-pancreatic-cancer-using-biological-feature-based-classification
#14
Huan-Jun Liu, Yuan-Ying Guo, Du-Jun Li
AIM: The use of saliva as a diagnostic fluid enables non-invasive sampling and thus is a prospective sample for disease tests. This study fully utilized the information from the salivary transcriptome to characterize pancreatic cancer related genes and predict novel salivary biomarkers. METHODS: We calculated the enrichment scores of gene ontology (GO) and pathways annotated in Kyoto Encyclopedia of Genes and Genomes database (KEGG) for pancreatic cancer-related genes...
April 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28098761/pancreatic-neuroendocrine-neoplasms-basic-biology-current-treatment-strategies-and-prospects-for-the-future
#15
REVIEW
Akihiro Ohmoto, Hirofumi Rokutan, Shinichi Yachida
Pancreatic neuroendocrine neoplasms (pNENs) are rare tumors accounting for only 1%-2% of all pancreatic tumors. pNENs are pathologically heterogeneous and are categorized into three groups (neuroendocrine tumor: NET G1, NET G2; and neuroendocrine carcinoma: NEC) on the basis of the Ki-67 proliferation index and the mitotic count according to the 2010 World Health Organization (WHO) classification of gastroenteropancreatic NENs. NEC in this classification includes both histologically well-differentiated and poorly differentiated subtypes, and modification of the WHO 2010 classification is under discussion based on genetic and clinical data...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27647802/next-generation-sequencing-adds-value-to-the-preoperative-diagnosis-of-pancreatic-cysts
#16
Matthew W Rosenbaum, Martin Jones, Jonathan C Dudley, Long P Le, A John Iafrate, Martha B Pitman
BACKGROUND: The diagnosis of a pancreatic cyst as mucinous or high-risk dictates the need for follow-up or surgery. Molecular analysis of aspirated pancreatic cyst fluid (PCF) can provide valuable information not obtained by carcinoembryonic antigen (CEA) analysis or cytology. METHODS: All patients who underwent molecular analysis of PCF between March 2013 and June 2015 were reviewed, including pathology, imaging, and follow-up. Molecular testing was performed using a patented, anchored multiplex polymerase chain reaction next-generation sequencing (NGS) platform, which sequenced numerous hotspots in 39 genes linked with malignancy...
January 2017: Cancer Cytopathology
https://www.readbyqxmd.com/read/27345450/-new-molecular-classification-of-colorectal-cancer-pancreatic-cancer-and-stomach-cancer-towards-%C3%A3-la-carte-treatment
#17
REVIEW
Chantal Dreyer, Pauline Afchain, Isabelle Trouilloud, Thierry André
This review reports 3 of recently published molecular classifications of the 3 main gastro-intestinal cancers: gastric, pancreatic and colorectal adenocarcinoma. In colorectal adenocarcinoma, 6 independent classifications were combined to finally hold 4 molecular sub-groups, Consensus Molecular Subtypes (CMS 1-4), linked to various clinical, molecular and survival data. CMS1 (14% MSI with immune activation); CMS2 (37%: canonical with epithelial differentiation and activation of the WNT/MYC pathway); CMS3 (13% metabolic with epithelial differentiation and RAS mutation); CMS4 (23%: mesenchymal with activation of TGFβ pathway and angiogenesis with stromal invasion)...
July 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/27225481/yin-yang-1-is-associated-with-cancer-stem-cell-transcription-factors-sox2-oct4-bmi1-and-clinical-implication
#18
REVIEW
Samantha Kaufhold, Hermes Garbán, Benjamin Bonavida
The transcription factor Yin Yang 1 (YY1) is frequently overexpressed in cancerous tissues compared to normal tissues and has regulatory roles in cell proliferation, cell viability, epithelial-mesenchymal transition, metastasis and drug/immune resistance. YY1 shares many properties with cancer stem cells (CSCs) that drive tumorigenesis, metastasis and drug resistance and are regulated by overexpression of certain transcription factors, including SOX2, OCT4 (POU5F1), BMI1 and NANOG. Based on these similarities, it was expected that YY1 expression would be associated with SOX2, OCT4, BMI1, and NANOG's expressions and activities...
May 25, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/26883357/genetics-and-biology-of-pancreatic-ductal-adenocarcinoma
#19
REVIEW
Haoqiang Ying, Prasenjit Dey, Wantong Yao, Alec C Kimmelman, Giulio F Draetta, Anirban Maitra, Ronald A DePinho
With 5-year survival rates remaining constant at 6% and rising incidences associated with an epidemic in obesity and metabolic syndrome, pancreatic ductal adenocarcinoma (PDAC) is on track to become the second most common cause of cancer-related deaths by 2030. The high mortality rate of PDAC stems primarily from the lack of early diagnosis and ineffective treatment for advanced tumors. During the past decade, the comprehensive atlas of genomic alterations, the prominence of specific pathways, the preclinical validation of such emerging targets, sophisticated preclinical model systems, and the molecular classification of PDAC into specific disease subtypes have all converged to illuminate drug discovery programs with clearer clinical path hypotheses...
February 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/26857392/relevance-of-sp-binding-site-polymorphism-in-wwox-for-treatment-outcome-in-pancreatic-cancer
#20
Markus A Schirmer, Claudia M Lüske, Sebastian Roppel, Alexander Schaudinn, Christian Zimmer, Ruben Pflüger, Martin Haubrock, Jacobe Rapp, Cenap Güngör, Maximilian Bockhorn, Thilo Hackert, Thomas Hank, Oliver Strobel, Jens Werner, Jakob R Izbicki, Steven A Johnsen, Jochen Gaedcke, Jürgen Brockmöller, B Michael Ghadimi
BACKGROUND: A genome-wide association study (GWAS) suggested inherited genetic single-nucleotide polymorphisms (SNPs) affecting overall survival (OS) in advanced pancreatic cancer. To identify robust clinical biomarkers, we tested the strongest reported candidate loci in an independent patient cohort, assessed cellular drug sensitivity, and evaluated molecular effects. METHODS: This study comprised 381 patients with histologically verified pancreatic ductal adenocarcinoma treated with gemcitabine-based chemotherapy...
May 2016: Journal of the National Cancer Institute
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