Recent updates of precision therapy for gastric cancer: Towards optimal tailored management

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13 Citations (Scopus)

Abstract

Signaling pathways of gastric carcinogenesis and gastric cancer progression are being avidly studied to seek optimal treatment of gastric cancer. Among them, hepatocyte growth factor (HGF)/c-MET, phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathways have been widely investigated. Their aberrant expression or mutation has been significantly associated with advanced stage or poor prognosis of gastric cancer. Recently, aberrations of immune checkpoints including programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) have been suggested as an important step in the formation of a microenvironment favorable for gastric cancer. Accomplishments in basic research have led to the development of novel agents targeting these signaling pathways. However, phase ? studies of selective anti-HGF/c-MET antibodies and mTOR inhibitor failed to show significant benefits in terms of overall survival and progression-free survival. Few agents directly targeting STAT3 have been developed. However, this target is still critical issue in terms of chemoresistance, and SH2-containing protein tyrosine phosphatase 1 might be a significant link to effectively inhibit STAT3 activity. Inhibition of PD-1/ PD-L1 showed durable efficacy in phase ? studies, and phase ? evaluation is warranted. Therapeutic strategy to concurrently inhibit multiple tyrosine kinases is a reasonable option, however, lapatinib needs to be further evaluated to identify good responders. Regorafenib has shown promising effectiveness in prolonging progression-free survival in a phase ? study. In this topic highlight, we review the biologic roles and outcomes of clinical studies targeting these signaling pathways.

Original languageEnglish
Pages (from-to)4638-4650
Number of pages13
JournalWorld Journal of Gastroenterology
Volume22
Issue number19
DOIs
Publication statusPublished - 2016 May 21

Fingerprint

Stomach Neoplasms
Hepatocyte Growth Factor
Sirolimus
CD274 Antigen
Disease-Free Survival
Janus Kinase 2
Protein Phosphatase 1
STAT3 Transcription Factor
Protein Tyrosine Phosphatases
1-Phosphatidylinositol 4-Kinase
Therapeutics
Protein-Tyrosine Kinases
Stomach
Carcinogenesis
Cell Death
Outcome Assessment (Health Care)
Mutation
Antibodies
Research

Keywords

  • Gastric cancer
  • Hepatocyte growth factor
  • Mammalian target of rapamycin
  • Programmed cell death ligand-1
  • Signal transducer and activator of transcription 3

ASJC Scopus subject areas

  • Gastroenterology

Cite this

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title = "Recent updates of precision therapy for gastric cancer: Towards optimal tailored management",
abstract = "Signaling pathways of gastric carcinogenesis and gastric cancer progression are being avidly studied to seek optimal treatment of gastric cancer. Among them, hepatocyte growth factor (HGF)/c-MET, phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathways have been widely investigated. Their aberrant expression or mutation has been significantly associated with advanced stage or poor prognosis of gastric cancer. Recently, aberrations of immune checkpoints including programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) have been suggested as an important step in the formation of a microenvironment favorable for gastric cancer. Accomplishments in basic research have led to the development of novel agents targeting these signaling pathways. However, phase ? studies of selective anti-HGF/c-MET antibodies and mTOR inhibitor failed to show significant benefits in terms of overall survival and progression-free survival. Few agents directly targeting STAT3 have been developed. However, this target is still critical issue in terms of chemoresistance, and SH2-containing protein tyrosine phosphatase 1 might be a significant link to effectively inhibit STAT3 activity. Inhibition of PD-1/ PD-L1 showed durable efficacy in phase ? studies, and phase ? evaluation is warranted. Therapeutic strategy to concurrently inhibit multiple tyrosine kinases is a reasonable option, however, lapatinib needs to be further evaluated to identify good responders. Regorafenib has shown promising effectiveness in prolonging progression-free survival in a phase ? study. In this topic highlight, we review the biologic roles and outcomes of clinical studies targeting these signaling pathways.",
keywords = "Gastric cancer, Hepatocyte growth factor, Mammalian target of rapamycin, Programmed cell death ligand-1, Signal transducer and activator of transcription 3",
author = "Joo, {Moon Kyung} and Park, {Jong Jae} and Hoon-Jai Chun",
year = "2016",
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T1 - Recent updates of precision therapy for gastric cancer

T2 - Towards optimal tailored management

AU - Joo, Moon Kyung

AU - Park, Jong Jae

AU - Chun, Hoon-Jai

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N2 - Signaling pathways of gastric carcinogenesis and gastric cancer progression are being avidly studied to seek optimal treatment of gastric cancer. Among them, hepatocyte growth factor (HGF)/c-MET, phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathways have been widely investigated. Their aberrant expression or mutation has been significantly associated with advanced stage or poor prognosis of gastric cancer. Recently, aberrations of immune checkpoints including programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) have been suggested as an important step in the formation of a microenvironment favorable for gastric cancer. Accomplishments in basic research have led to the development of novel agents targeting these signaling pathways. However, phase ? studies of selective anti-HGF/c-MET antibodies and mTOR inhibitor failed to show significant benefits in terms of overall survival and progression-free survival. Few agents directly targeting STAT3 have been developed. However, this target is still critical issue in terms of chemoresistance, and SH2-containing protein tyrosine phosphatase 1 might be a significant link to effectively inhibit STAT3 activity. Inhibition of PD-1/ PD-L1 showed durable efficacy in phase ? studies, and phase ? evaluation is warranted. Therapeutic strategy to concurrently inhibit multiple tyrosine kinases is a reasonable option, however, lapatinib needs to be further evaluated to identify good responders. Regorafenib has shown promising effectiveness in prolonging progression-free survival in a phase ? study. In this topic highlight, we review the biologic roles and outcomes of clinical studies targeting these signaling pathways.

AB - Signaling pathways of gastric carcinogenesis and gastric cancer progression are being avidly studied to seek optimal treatment of gastric cancer. Among them, hepatocyte growth factor (HGF)/c-MET, phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathways have been widely investigated. Their aberrant expression or mutation has been significantly associated with advanced stage or poor prognosis of gastric cancer. Recently, aberrations of immune checkpoints including programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) have been suggested as an important step in the formation of a microenvironment favorable for gastric cancer. Accomplishments in basic research have led to the development of novel agents targeting these signaling pathways. However, phase ? studies of selective anti-HGF/c-MET antibodies and mTOR inhibitor failed to show significant benefits in terms of overall survival and progression-free survival. Few agents directly targeting STAT3 have been developed. However, this target is still critical issue in terms of chemoresistance, and SH2-containing protein tyrosine phosphatase 1 might be a significant link to effectively inhibit STAT3 activity. Inhibition of PD-1/ PD-L1 showed durable efficacy in phase ? studies, and phase ? evaluation is warranted. Therapeutic strategy to concurrently inhibit multiple tyrosine kinases is a reasonable option, however, lapatinib needs to be further evaluated to identify good responders. Regorafenib has shown promising effectiveness in prolonging progression-free survival in a phase ? study. In this topic highlight, we review the biologic roles and outcomes of clinical studies targeting these signaling pathways.

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KW - Signal transducer and activator of transcription 3

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