mTOR as a therapeutic target in patients with gastric cancer
The poor long‐term outcomes associated with current chemotherapy treatment of patients with advanced gastric cancer suggest a need for novel targeted agents that may confer a better survival benefit. Evidence of mammalian target of rapamycin (mTOR) activation has been demonstrated in patient‐derived...
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| Veröffentlicht in: | International journal of cancer 2012-02, Vol.130 (3), p.491-496 |
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| container_title | International journal of cancer |
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| creator | Al-Batran, Salah-Eddin Ducreux, Michel Ohtsu, Atsushi |
| description | The poor long‐term outcomes associated with current chemotherapy treatment of patients with advanced gastric cancer suggest a need for novel targeted agents that may confer a better survival benefit. Evidence of mammalian target of rapamycin (mTOR) activation has been demonstrated in patient‐derived gastric cancer cells and tumors. This review explores the relevance of the mTOR pathway to gastric cancer pathogenesis and its potential as a therapeutic target in patients with gastric cancer as well as presenting the first available clinical data on mTOR inhibitors in this disease setting. Preclinical data suggest that suppression of the mTOR pathway inhibited the proliferation of gastric cancer cells and delayed tumor progression in in vitro and animal models. In the clinical setting, the mTOR inhibitor everolimus has been active and well tolerated in phase I/II studies of patients with chemotherapy‐refractory metastatic gastric cancer. Based on these promising results, everolimus currently is being investigated as a monotherapy or in combination with chemotherapeutic agents in ongoing phase II/III clinical studies. |
| doi_str_mv | 10.1002/ijc.26396 |
| format | Article |
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Evidence of mammalian target of rapamycin (mTOR) activation has been demonstrated in patient‐derived gastric cancer cells and tumors. This review explores the relevance of the mTOR pathway to gastric cancer pathogenesis and its potential as a therapeutic target in patients with gastric cancer as well as presenting the first available clinical data on mTOR inhibitors in this disease setting. Preclinical data suggest that suppression of the mTOR pathway inhibited the proliferation of gastric cancer cells and delayed tumor progression in in vitro and animal models. In the clinical setting, the mTOR inhibitor everolimus has been active and well tolerated in phase I/II studies of patients with chemotherapy‐refractory metastatic gastric cancer. Based on these promising results, everolimus currently is being investigated as a monotherapy or in combination with chemotherapeutic agents in ongoing phase II/III clinical studies.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.26396</identifier><identifier>PMID: 21898386</identifier><identifier>CODEN: IJCNAW</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Biological and medical sciences ; Cancer ; Chemotherapy ; Everolimus ; gastric adenocarcinoma ; Gastric cancer ; Gastroenterology. Liver. Pancreas. Abdomen ; Humans ; Medical research ; Medical sciences ; Molecular Targeted Therapy ; mTOR ; mTOR inhibitors ; Protein Kinase Inhibitors - pharmacology ; Protein Kinase Inhibitors - therapeutic use ; Signal Transduction - drug effects ; Sirolimus - analogs & derivatives ; Sirolimus - pharmacology ; Sirolimus - therapeutic use ; Stomach Neoplasms - drug therapy ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; TOR Serine-Threonine Kinases - antagonists & inhibitors ; Tumors</subject><ispartof>International journal of cancer, 2012-02, Vol.130 (3), p.491-496</ispartof><rights>Copyright © 2011 UICC</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 UICC.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4556-c4db4e431279ba565da9d8baae3d112f3981d62663a536d3395b1bacf19e307c3</citedby><cites>FETCH-LOGICAL-c4556-c4db4e431279ba565da9d8baae3d112f3981d62663a536d3395b1bacf19e307c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fijc.26396$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fijc.26396$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25533424$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21898386$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Al-Batran, Salah-Eddin</creatorcontrib><creatorcontrib>Ducreux, Michel</creatorcontrib><creatorcontrib>Ohtsu, Atsushi</creatorcontrib><title>mTOR as a therapeutic target in patients with gastric cancer</title><title>International journal of cancer</title><addtitle>Int. J. Cancer</addtitle><description>The poor long‐term outcomes associated with current chemotherapy treatment of patients with advanced gastric cancer suggest a need for novel targeted agents that may confer a better survival benefit. Evidence of mammalian target of rapamycin (mTOR) activation has been demonstrated in patient‐derived gastric cancer cells and tumors. This review explores the relevance of the mTOR pathway to gastric cancer pathogenesis and its potential as a therapeutic target in patients with gastric cancer as well as presenting the first available clinical data on mTOR inhibitors in this disease setting. Preclinical data suggest that suppression of the mTOR pathway inhibited the proliferation of gastric cancer cells and delayed tumor progression in in vitro and animal models. In the clinical setting, the mTOR inhibitor everolimus has been active and well tolerated in phase I/II studies of patients with chemotherapy‐refractory metastatic gastric cancer. Based on these promising results, everolimus currently is being investigated as a monotherapy or in combination with chemotherapeutic agents in ongoing phase II/III clinical studies.</description><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Cancer</subject><subject>Chemotherapy</subject><subject>Everolimus</subject><subject>gastric adenocarcinoma</subject><subject>Gastric cancer</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Humans</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Molecular Targeted Therapy</subject><subject>mTOR</subject><subject>mTOR inhibitors</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Protein Kinase Inhibitors - therapeutic use</subject><subject>Signal Transduction - drug effects</subject><subject>Sirolimus - analogs & derivatives</subject><subject>Sirolimus - pharmacology</subject><subject>Sirolimus - therapeutic use</subject><subject>Stomach Neoplasms - drug therapy</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>TOR Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>Tumors</subject><issn>0020-7136</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10N9rFDEQB_Agij1PH_wHZEFEfNg2k9lkN-CLHNoflJZKteBLmM1m25x7e2eSpfa_N3rXCoIvycN8Zib5MvYS-D5wLg780u4LhVo9YjPgui65APmYzXKNlzWg2mPPYlxyDiB59ZTtCWh0g42asfery_PPBcWCinTjAm3clLwtEoVrlwo_FhtK3o0pFrc-3RTXFFPIdUujdeE5e9LTEN2L3T1nXz59vFwclafnh8eLD6elraRU-ezaylUIotYtSSU70l3TEjnsAESPuoFOCaWQJKoOUcsWWrI9aIe8tjhnb7dzN2H9Y3IxmZWP1g0DjW49RaO5AilE_umcvf5HLtdTGPPjDMiq0oqjFlm92yob1jEG15tN8CsKdwa4-Z2oyYmaP4lm-2o3cWpXrnuQ9xFm8GYHKFoa-pCj8fGvkxKxElV2B1t36wd39_-N5vhkcb-63Hb4mNzPhw4K342qsZbm6uzQXFx8PRFn367MEf4CjXWZoA</recordid><startdate>20120201</startdate><enddate>20120201</enddate><creator>Al-Batran, Salah-Eddin</creator><creator>Ducreux, Michel</creator><creator>Ohtsu, Atsushi</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Blackwell</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20120201</creationdate><title>mTOR as a therapeutic target in patients with gastric cancer</title><author>Al-Batran, Salah-Eddin ; Ducreux, Michel ; Ohtsu, Atsushi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4556-c4db4e431279ba565da9d8baae3d112f3981d62663a536d3395b1bacf19e307c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Cancer</topic><topic>Chemotherapy</topic><topic>Everolimus</topic><topic>gastric adenocarcinoma</topic><topic>Gastric cancer</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Humans</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Molecular Targeted Therapy</topic><topic>mTOR</topic><topic>mTOR inhibitors</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Protein Kinase Inhibitors - therapeutic use</topic><topic>Signal Transduction - drug effects</topic><topic>Sirolimus - analogs & derivatives</topic><topic>Sirolimus - pharmacology</topic><topic>Sirolimus - therapeutic use</topic><topic>Stomach Neoplasms - drug therapy</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>TOR Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Al-Batran, Salah-Eddin</creatorcontrib><creatorcontrib>Ducreux, Michel</creatorcontrib><creatorcontrib>Ohtsu, Atsushi</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Al-Batran, Salah-Eddin</au><au>Ducreux, Michel</au><au>Ohtsu, Atsushi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>mTOR as a therapeutic target in patients with gastric cancer</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int. 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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Biological and medical sciences Cancer Chemotherapy Everolimus gastric adenocarcinoma Gastric cancer Gastroenterology. Liver. Pancreas. Abdomen Humans Medical research Medical sciences Molecular Targeted Therapy mTOR mTOR inhibitors Protein Kinase Inhibitors - pharmacology Protein Kinase Inhibitors - therapeutic use Signal Transduction - drug effects Sirolimus - analogs & derivatives Sirolimus - pharmacology Sirolimus - therapeutic use Stomach Neoplasms - drug therapy Stomach. Duodenum. Small intestine. Colon. Rectum. Anus TOR Serine-Threonine Kinases - antagonists & inhibitors Tumors |
| title | mTOR as a therapeutic target in patients with gastric cancer |
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