Updates In GC

1. Title: Updates in Gastric Cancer
By: Samieh Asadian
1

2. 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
2

3. INTRODUCTION
Pathogen
Environmenta
l factors
Host
immune
system
Host
genetic
alterations
3
GC is a
multifactorial
disease

4. 4
https://www.researchgate.net/figure/269096725_fig3_Fig-3-From-
normal-stomach-to-gastric-cancer-and-relation-with-gastric-acid-
secretion

5. 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)
5

6. MOLECULAR DETERMINANTS OF GASTRIC CANCER INVASION
AND 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
6

7. MOLECULAR CHANGES ASSOCIATED WITH H. PYLORI INFECTION
CagA(+) H. pylori
infection
Cag T4SS
Vag A(+) H.pylori
infection
Lipopolycacharids
7

8. EMT
8
DOI: 10.4251/wjgo.v8.i2.147
World J Gastrointest Oncology

9. ROLE OF HELICOBACTER PYLORI IN GASTRIC CANCER
9
DOI: 10.4251/wjgo.v8.i2.147
World J Gastrointest Oncology

10. ROLE OF HELICOBACTER PYLORI IN GASTRIC CANCER
10
DOI: 10.4251/wjgo.v8.i2.147
World J Gastrointest Oncology

11. CHARACTERIZATION OF GASTRIC CANCER
11
DOI: 10.1177/1756283X12453636
TRMOME 1136 No. of Pages 11 ,Trends In Molecular
Medicine. Cell Press.

12. KEY FEATURES OF GASTRIC CANCER SUBTYPES ACCORDING TO THE CANCER GENOME ATLAS
(TCGA)
12
http://dx.doi.org/10.1038/nrclinonc.2016.15
NATURE REVIEWS | CLINICAL ONCOLOGY

13. TARGETED THERAPY IN GASTRIC CANCER
13
Nature Reviews Clinical Oncology 10, 643
655(2013) doi:10.1038/nrclinonc.2013.170

14. TARGETED AGENTS REACHING CLINICAL DEVELOPMENT
14
Ther Adv Gastroenterol(2013) 6(1) 15–31.
DOI:10.1177/1756283X12453636

15. ANGIOGENIC SIGNALLING NETWORK AND INHIBITION BY ANTIANGIOGENIC DRUGS
15
http://dx.doi.org/10.1038/nrclinonc.2016.15
NATURE REVIEWS | CLINICAL ONCOLOGY

16. DISCOVERY OF BIOMARKERS FOR GASTRIC CANCER
16
doi:10.1016/j.jprot.2012.03.046
1874-3919/$ – see front matter © 2012 Elsevier B.V. All rights reserved.

17. TYPES OF HUMAN NONCODING RNAS IN GASTRIC CANCER
17
Hindawi Publishing Corporation .Disease Markers .Volume 2015, Article ID 503762, 14 pages
http://dx.doi.org/10.1155/2015/503762

18. A NOVEL HUMAN GASTRIC PRIMARY CELL CULTURE SYSTEM
18
Nature Cell Biology 18, 246254 (2016) doi:10.1038/ncb3312

19. 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.
19