updates in gastric cancer
TRANSCRIPT
Title: Updates in Gastric Cancer
By: Samieh Asadian 1
CONTENT Introduction Molecular genetics of gastric cancer Molecular determinants of gastric cancer invasion and metastasis Molecular changes associated with H. pylori infection characterization of gastric cancer Targeted therapy in gastric cancer Targeted agents reaching clinical development Angiogenic signalling network and inhibition by antiangiogenic drugs Discovery of biomarkers for gastric cancer Types of human noncoding RNAs in gastric cancer A novel human gastric primary cell culture system
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INTRODUCTION
Pathogen
Environmental
factors
Host immune system
Host genetic
alterations
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GC is a multifactoria
l disease
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https://www.researchgate.net/figure/269096725_fig3_Fig-3-From-normal-stomach-to-gastric-cancer-and-relation-with-
gastric-acid-secretion
MOLECULAR GENETICS OF GASTRIC CANCER
Inactivation of tumor suppressor genes
• inactivation of p53 and p16• (APC) gene mutations
• fragile histidine triad (FHIT)• deleted in colon cancer (DCC)
• transcriptional silencing of various genes (e.g., Ecadherin,p16, p15,
MGMT, and hMLH1)
Activation of oncogenes• c-met proto oncogene
• c-erB2 (HER-2/neu) gene• c-erbB3, K-sam,Ras, and c-myc,
Telomerase reactivation
MSI* High frequency (MSI-H)
* low-frequency (MSI-L)
* stable (MSS)
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MOLECULAR DETERMINANTS OF GASTRIC CANCER INVASIONAND METASTASIS
Alterations of growth factors and cytokines• Epidermal growth factor (EGF)
family• Vascular endothelial growth factor
(VEGF)• insulin-like growth factor (IGF)
• numerous cytokines, such as TGF, IL-1,and IL-8
Apoptosis and cell-cycle regulators
• Genes that regulate apoptosis, such as FAS, tumor necrosis
factor(TNF), and bcl-2, contribute to the development of cancer
• LOH at the bcl-2 locus
Alterations of adhesion molecules
• E-cadherin
• Nitric oxide synthase (NOS)
• Cyclooxygenase (COX)-2
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MOLECULAR CHANGES ASSOCIATED WITH H. PYLORI INFECTION
CagA(+) H. pylori infection
Cag T4SS
Vag A(+) H.pylori infection
Lipo polysacarids
EMT
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DOI: 10.4251/wjgo.v8.i2.147World J Gastrointest Oncology
ROLE OF HELICOBACTER PYLORI IN GASTRIC CANCER
9DOI: 10.4251/wjgo.v8.i2.147
World J Gastrointest Oncology
ROLE OF HELICOBACTER PYLORI IN GASTRIC CANCER
10DOI: 10.4251/wjgo.v8.i2.147
World J Gastrointest Oncology
CHARACTERIZATION OF GASTRIC CANCER
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DOI: 10.1177/1756283X12453636TRMOME 1136 No. of Pages 11 ,Trends In
Molecular Medicine. Cell Press.
KEY FEATURES OF GASTRIC CANCER SUBTYPES ACCORDING TO THE CANCER GENOME ATLAS (TCGA)
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http://dx.doi.org/10.1038/nrclinonc.2016.15 NATURE REVIEWS | CLINICAL ONCOLOGY
TARGETED THERAPY IN GASTRIC CANCER
13Nature Reviews Clinical Oncology 10, 643
655(2013) doi:10.1038/nrclinonc.2013.170
TARGETED AGENTS REACHING CLINICAL DEVELOPMENT
14Ther Adv Gastroenterol(2013) 6(1) 15–31.
DOI:10.1177/1756283X12453636
ANGIOGENIC SIGNALLING NETWORK AND INHIBITION BY ANTIANGIOGENIC DRUGS
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http://dx.doi.org/10.1038/nrclinonc.2016.15 NATURE REVIEWS | CLINICAL ONCOLOGY
DISCOVERY OF BIOMARKERS FOR GASTRIC CANCER
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doi:10.1016/j.jprot.2012.03.0461874-3919/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
TYPES OF HUMAN NONCODING RNAS IN GASTRIC CANCER
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Hindawi Publishing Corporation .Disease Markers .Volume 2015, Article ID 503762, 14 pages http://dx.doi.org/10.1155/2015/503762
A NOVEL HUMAN GASTRIC PRIMARY CELL CULTURE SYSTEM
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Nature Cell Biology 18, 246254 (2016) doi:10.1038/ncb3312
R E F E R E N C E S NATURE REVIEWS | CLINICAL ONCOLOGY .Clinical impact of tumour biology in the
management of gastroesophageal cancer. 2016 Macmillan Publishers Limited. All rights reserved.
Wadhwa, R. et al. Nat. Rev. Clin. Oncol. advance online publication 24 September 2013; Gastric cancer—molecular and clinical dimensions .
J O U R N A L O F P R O T E O M I C S 7 5 ( 2 0 1 2 ) 3 0 8 1 – 3 0 9 7. Discovery of biomarkers for gastric cancer:A proteomics approach.
Gastric Cancer (2004) 7: 61–77. Molecular basis of gastric cancer development and progression. International and Japanese Gastric Cancer Associations.
World J Gastrointest Oncol 2016 February 15; 8(2): 147-158 ISSN 1948-5204. Role of Helicobacter pylori in gastric cancer: Updates.
Ther Adv Gastroenterol(2013) 6(1) 15–31. Molecular targeted therapies in advanced gastric cancer: does tumor histology matter?
Trends in Molecular Medicine, Month Year, Vol. xx, No. yy . © 2016 Elsevier Ltd. All rights reserved.How CanGastricCancer MolecularProfiling Guide Future Therapies?
Nature Cell Biology 18, 246–254 (2016) doi:10.1038/ncb3312Published online 25 February 2016. Organoids as an in vitro model of human development and disease.
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