Advances in Targeting the Ras/Raf/MEK/Erk Mitogen-Activated Protein Kinase Cascade with MEK Inhibitors for Cancer Therapy
The identification of intracellular signaling cascades important for the growth and survival of cancer cells has led to the development of targeted cancer therapeutics aimed at blocking these signals. The mitogen-activated protein kinase (MAPK) pathway has a well-defined role in cancer biology and h...
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| Veröffentlicht in: | Clinical cancer research 2008-01, Vol.14 (2), p.342-346 |
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| container_title | Clinical cancer research |
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| creator | FRIDAY, Bret B ADJEI, Alex A |
| description | The identification of intracellular signaling cascades important for the growth and survival of cancer cells has led to the
development of targeted cancer therapeutics aimed at blocking these signals. The mitogen-activated protein kinase (MAPK) pathway
has a well-defined role in cancer biology and has been an important target in the development of targeted therapies. Recently,
several small-molecule inhibitors of MAPK/extracellular signal–regulated kinase kinase (MEK), a key intermediary of MAPK signaling,
have been developed and are currently being tested in clinical trials. Herein, we review the MAPK pathway, the development
of small-molecule MEK inhibitors, and the results obtained to date with MEK inhibitors in human cancer trials. |
| doi_str_mv | 10.1158/1078-0432.CCR-07-4790 |
| format | Article |
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has a well-defined role in cancer biology and has been an important target in the development of targeted therapies. Recently,
several small-molecule inhibitors of MAPK/extracellular signal–regulated kinase kinase (MEK), a key intermediary of MAPK signaling,
have been developed and are currently being tested in clinical trials. Herein, we review the MAPK pathway, the development
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development of targeted cancer therapeutics aimed at blocking these signals. The mitogen-activated protein kinase (MAPK) pathway
has a well-defined role in cancer biology and has been an important target in the development of targeted therapies. Recently,
several small-molecule inhibitors of MAPK/extracellular signal–regulated kinase kinase (MEK), a key intermediary of MAPK signaling,
have been developed and are currently being tested in clinical trials. Herein, we review the MAPK pathway, the development
of small-molecule MEK inhibitors, and the results obtained to date with MEK inhibitors in human cancer trials.</description><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Enzyme Inhibitors - therapeutic use</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Humans</subject><subject>map kinase</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Medical sciences</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - enzymology</subject><subject>Pharmacology. Drug treatments</subject><subject>raf kinase</subject><subject>raf Kinases - metabolism</subject><subject>ras Proteins - metabolism</subject><subject>signal transduction</subject><subject>Small Molecule Libraries - pharmacology</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV1v0zAUhi3ExMbgJ4B8w7jK6s84uayiwqZtAlXl2nKc48bQJsV2N_Xf46wFLndlS35en6PnRegDJdeUympGiaoKIji7bpplQVQhVE1eoQsqpSo4K-XrfP_LnKO3Mf4khApKxBt0TivGOCPlBTrMu0czWIjYD3hlwhqSH9Y49YCXJs6Wxs0eFnezRfiFH3wa1zAUc5v8o0nQ4e9hTJBzd34wEXBjojUd4CefepxT-HbofZtTIWI3hvyeBwW86iGY3eEdOnNmE-H96bxEP74sVs1Ncf_t620zvy-sECoVhrGOc0NBUEdMLUXpaMsrJgmXNZS1VaptKWNSVqyWyqkqw7KlnepY5YDwS3R1_HcXxt97iElvfbSw2ZgBxn3UijChSqJeBBmRtaD1BMojaMMYYwCnd8FvTThoSvRUjp7E60m8zuVoovRUTs59PA3Yt1vo_qdObWTg0wmYTG5cyMJ8_Mex3J-o6LTA5yPX-3X_5ANo-6w2QAQTbK-p0ExzwfgfFMKjhw</recordid><startdate>20080115</startdate><enddate>20080115</enddate><creator>FRIDAY, Bret B</creator><creator>ADJEI, Alex A</creator><general>American Association for Cancer Research</general><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>7TO</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20080115</creationdate><title>Advances in Targeting the Ras/Raf/MEK/Erk Mitogen-Activated Protein Kinase Cascade with MEK Inhibitors for Cancer Therapy</title><author>FRIDAY, Bret B ; ADJEI, Alex A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c447t-a22d33a1e41f0a9546f1b38250359e69c77bb1225582957f783a15b1d7d28fe03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Enzyme Inhibitors - therapeutic use</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Humans</topic><topic>map kinase</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Medical sciences</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - enzymology</topic><topic>Pharmacology. Drug treatments</topic><topic>raf kinase</topic><topic>raf Kinases - metabolism</topic><topic>ras Proteins - metabolism</topic><topic>signal transduction</topic><topic>Small Molecule Libraries - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>FRIDAY, Bret B</creatorcontrib><creatorcontrib>ADJEI, Alex A</creatorcontrib><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>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>FRIDAY, Bret B</au><au>ADJEI, Alex A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Advances in Targeting the Ras/Raf/MEK/Erk Mitogen-Activated Protein Kinase Cascade with MEK Inhibitors for Cancer Therapy</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2008-01-15</date><risdate>2008</risdate><volume>14</volume><issue>2</issue><spage>342</spage><epage>346</epage><pages>342-346</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>The identification of intracellular signaling cascades important for the growth and survival of cancer cells has led to the
development of targeted cancer therapeutics aimed at blocking these signals. The mitogen-activated protein kinase (MAPK) pathway
has a well-defined role in cancer biology and has been an important target in the development of targeted therapies. Recently,
several small-molecule inhibitors of MAPK/extracellular signal–regulated kinase kinase (MEK), a key intermediary of MAPK signaling,
have been developed and are currently being tested in clinical trials. Herein, we review the MAPK pathway, the development
of small-molecule MEK inhibitors, and the results obtained to date with MEK inhibitors in human cancer trials.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>18223206</pmid><doi>10.1158/1078-0432.CCR-07-4790</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Clinical cancer research, 2008-01, Vol.14 (2), p.342-346 |
| issn | 1078-0432 1557-3265 |
| language | eng |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Antineoplastic agents Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Biological and medical sciences Enzyme Inhibitors - pharmacology Enzyme Inhibitors - therapeutic use Extracellular Signal-Regulated MAP Kinases - metabolism Humans map kinase MAP Kinase Signaling System - drug effects Medical sciences Mitogen-Activated Protein Kinases - metabolism Neoplasms - drug therapy Neoplasms - enzymology Pharmacology. Drug treatments raf kinase raf Kinases - metabolism ras Proteins - metabolism signal transduction Small Molecule Libraries - pharmacology |
| title | Advances in Targeting the Ras/Raf/MEK/Erk Mitogen-Activated Protein Kinase Cascade with MEK Inhibitors for Cancer Therapy |
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