Updates in Gastric Cancer

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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