Small molecules and targeted therapies in distant metastatic disease
Identifieur interne : 002090 ( Pmc/Curation ); précédent : 002089; suivant : 002091Small molecules and targeted therapies in distant metastatic disease
Auteurs : P. Hersey [Australie] ; L. Bastholt [Danemark] ; V. Chiarion-Sileni [Italie] ; G. Cinat [Argentine] ; R. Dummer [Suisse] ; A. M. M. Eggermont [Pays-Bas] ; E. Espinosa [Espagne] ; A. Hauschild [Allemagne] ; I. Quirt [Canada] ; C. Robert [France] ; D. Schadendorf [Allemagne]Source :
- Annals of Oncology [ 0923-7534 ] ; 2009.
Abstract
Chemotherapy, biological agents or combinations of both have had little impact on survival of patients with metastatic melanoma. Advances in understanding the genetic changes associated with the development of melanoma resulted in availability of promising new agents that inhibit specific proteins up-regulated in signal cell pathways or inhibit anti-apoptotic proteins. Sorafenib, a multikinase inhibitor of the RAF/RAS/MEK pathway, elesclomol (STA-4783) and oblimersen (G3139), an antisense oligonucleotide targeting anti-apoptotic BCl-2, are in phase III clinical studies in combination with chemotherapy. Agents targeting mutant B-Raf (RAF265 and PLX4032), MEK (PD0325901, AZD6244), heat-shock protein 90 (tanespimycin), mTOR (everolimus, deforolimus, temsirolimus) and VEGFR (axitinib) showed some promise in earlier stages of clinical development. Receptor tyrosine-kinase inhibitors (imatinib, dasatinib, sunitinib) may have a role in treatment of patients with melanoma harbouring c-Kit mutations. Although often studied as single agents with disappointing results, new targeted drugs should be more thoroughly evaluated in combination therapies. The future of rational use of new targeted agents also depends on successful application of analytical techniques enabling molecular profiling of patients and leading to selection of likely therapy responders.
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DOI: 10.1093/annonc/mdp254
PubMed: 19617296
PubMed Central: 2712592
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Cinat</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Oncology, Instituto de Oncologia Angel Roffo, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea>Department of Oncology, Instituto de Oncologia Angel Roffo, Buenos Aires</wicri:regionArea></affiliation></author><author><name sortKey="Dummer, R" sort="Dummer, R" uniqKey="Dummer R" first="R." last="Dummer">R. Dummer</name><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Dermatology, University of Zurich Hospital, Zurich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Dermatology, University of Zurich Hospital, Zurich</wicri:regionArea></affiliation></author><author><name sortKey="Eggermont, A M M" sort="Eggermont, A M M" uniqKey="Eggermont A" first="A. M. M." last="Eggermont">A. M. M. 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Schadendorf</name><affiliation wicri:level="1"><nlm:aff id="aff11">Department of Dermatology, University Hospital Essen, Essen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, University Hospital Essen, Essen</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19617296</idno><idno type="pmc">2712592</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712592</idno><idno type="RBID">PMC:2712592</idno><idno type="doi">10.1093/annonc/mdp254</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">002240</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002240</idno><idno type="wicri:Area/Pmc/Curation">002090</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002090</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Small molecules and targeted therapies in distant metastatic disease</title><author><name sortKey="Hersey, P" sort="Hersey, P" uniqKey="Hersey P" first="P." last="Hersey">P. Hersey</name><affiliation wicri:level="1"><nlm:aff id="aff1">Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, New South Wales, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, New South Wales</wicri:regionArea></affiliation></author><author><name sortKey="Bastholt, L" sort="Bastholt, L" uniqKey="Bastholt L" first="L." last="Bastholt">L. Bastholt</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Oncology, Odense University Hospital, Odense, Denmark</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Department of Oncology, Odense University Hospital, Odense</wicri:regionArea></affiliation></author><author><name sortKey="Chiarion Sileni, V" sort="Chiarion Sileni, V" uniqKey="Chiarion Sileni V" first="V." last="Chiarion-Sileni">V. 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Dummer</name><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Dermatology, University of Zurich Hospital, Zurich, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Dermatology, University of Zurich Hospital, Zurich</wicri:regionArea></affiliation></author><author><name sortKey="Eggermont, A M M" sort="Eggermont, A M M" uniqKey="Eggermont A" first="A. M. M." last="Eggermont">A. M. M. Eggermont</name><affiliation wicri:level="1"><nlm:aff id="aff6">Department of Surgical Oncology, Erasmus University Medical Center–Daniel den Hoed Cancer Center, Rotterdam, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Surgical Oncology, Erasmus University Medical Center–Daniel den Hoed Cancer Center, Rotterdam</wicri:regionArea></affiliation></author><author><name sortKey="Espinosa, E" sort="Espinosa, E" uniqKey="Espinosa E" first="E." last="Espinosa">E. Espinosa</name><affiliation wicri:level="1"><nlm:aff id="aff7">Department of Oncology, Hospital La Paz, Madrid, Spain</nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Oncology, Hospital La Paz, Madrid</wicri:regionArea></affiliation></author><author><name sortKey="Hauschild, A" sort="Hauschild, A" uniqKey="Hauschild A" first="A." last="Hauschild">A. Hauschild</name><affiliation wicri:level="1"><nlm:aff id="aff8">Department of Dermatology, University of Kiel, Kiel, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, University of Kiel, Kiel</wicri:regionArea></affiliation></author><author><name sortKey="Quirt, I" sort="Quirt, I" uniqKey="Quirt I" first="I." last="Quirt">I. Quirt</name><affiliation wicri:level="1"><nlm:aff id="aff9">Princess Margaret Hospital, Toronto, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Princess Margaret Hospital, Toronto</wicri:regionArea></affiliation></author><author><name sortKey="Robert, C" sort="Robert, C" uniqKey="Robert C" first="C." last="Robert">C. Robert</name><affiliation wicri:level="1"><nlm:aff id="aff10">Department of Dermatology, Institut Gustave Roussy, Villejuif, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Department of Dermatology, Institut Gustave Roussy, Villejuif</wicri:regionArea></affiliation></author><author><name sortKey="Schadendorf, D" sort="Schadendorf, D" uniqKey="Schadendorf D" first="D." last="Schadendorf">D. Schadendorf</name><affiliation wicri:level="1"><nlm:aff id="aff11">Department of Dermatology, University Hospital Essen, Essen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, University Hospital Essen, Essen</wicri:regionArea></affiliation></author></analytic><series><title level="j">Annals of Oncology</title><idno type="ISSN">0923-7534</idno><idno type="eISSN">1569-8041</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Chemotherapy, biological agents or combinations of both have had little impact on survival of patients with metastatic melanoma. Advances in understanding the genetic changes associated with the development of melanoma resulted in availability of promising new agents that inhibit specific proteins up-regulated in signal cell pathways or inhibit anti-apoptotic proteins. Sorafenib, a multikinase inhibitor of the RAF/RAS/MEK pathway, elesclomol (STA-4783) and oblimersen (G3139), an antisense oligonucleotide targeting anti-apoptotic BCl-2, are in phase III clinical studies in combination with chemotherapy. Agents targeting mutant B-Raf (RAF265 and PLX4032), MEK (PD0325901, AZD6244), heat-shock protein 90 (tanespimycin), mTOR (everolimus, deforolimus, temsirolimus) and VEGFR (axitinib) showed some promise in earlier stages of clinical development. Receptor tyrosine-kinase inhibitors (imatinib, dasatinib, sunitinib) may have a role in treatment of patients with melanoma harbouring c-Kit mutations. Although often studied as single agents with disappointing results, new targeted drugs should be more thoroughly evaluated in combination therapies. The future of rational use of new targeted agents also depends on successful application of analytical techniques enabling molecular profiling of patients and leading to selection of likely therapy responders.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Khayat, D" uniqKey="Khayat D">D Khayat</name></author><author><name sortKey="Meric, J B" uniqKey="Meric J">J-B Meric</name></author><author><name sortKey="Rixie, O" uniqKey="Rixie O">O Rixie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tsao, H" uniqKey="Tsao H">H Tsao</name></author><author><name sortKey="Atkins, Mb" uniqKey="Atkins M">MB Atkins</name></author><author><name sortKey="Sober, Aj" uniqKey="Sober A">AJ Sober</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tawbi, Ha" uniqKey="Tawbi H">HA Tawbi</name></author><author><name sortKey="Kirkwood, Jm" uniqKey="Kirkwood J">JM 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Ann Oncol</journal-id><journal-id journal-id-type="iso-abbrev">Ann. Oncol</journal-id><journal-id journal-id-type="hwp">annonc</journal-id><journal-id journal-id-type="publisher-id">annonc</journal-id><journal-title-group><journal-title>Annals of Oncology</journal-title></journal-title-group><issn pub-type="ppub">0923-7534</issn><issn pub-type="epub">1569-8041</issn><publisher><publisher-name>Oxford University Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">19617296</article-id><article-id pub-id-type="pmc">2712592</article-id><article-id pub-id-type="doi">10.1093/annonc/mdp254</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group></article-categories><title-group><article-title>Small molecules and targeted therapies in distant metastatic disease</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Hersey</surname><given-names>P.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib><contrib contrib-type="author"><name><surname>Bastholt</surname><given-names>L.</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Chiarion-Sileni</surname><given-names>V.</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Cinat</surname><given-names>G.</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Dummer</surname><given-names>R.</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Eggermont</surname><given-names>A. M. M.</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Espinosa</surname><given-names>E.</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name><surname>Hauschild</surname><given-names>A.</given-names></name><xref ref-type="aff" rid="aff8">8</xref></contrib><contrib contrib-type="author"><name><surname>Quirt</surname><given-names>I.</given-names></name><xref ref-type="aff" rid="aff9">9</xref></contrib><contrib contrib-type="author"><name><surname>Robert</surname><given-names>C.</given-names></name><xref ref-type="aff" rid="aff10">10</xref></contrib><contrib contrib-type="author"><name><surname>Schadendorf</surname><given-names>D.</given-names></name><xref ref-type="aff" rid="aff11">11</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Immunology and Oncology Unit, Calvary Mater Newcastle Hospital, New South Wales, Australia</aff><aff id="aff2"><label>2</label>Department of Oncology, Odense University Hospital, Odense, Denmark</aff><aff id="aff3"><label>3</label>Department of Oncology, Istituto Oncologico Veneto, Padova, Italy</aff><aff id="aff4"><label>4</label>Department of Oncology, Instituto de Oncologia Angel Roffo, Buenos Aires, Argentina</aff><aff id="aff5"><label>5</label>Department of Dermatology, University of Zurich Hospital, Zurich, Switzerland</aff><aff id="aff6"><label>6</label>Department of Surgical Oncology, Erasmus University Medical Center–Daniel den Hoed Cancer Center, Rotterdam, The Netherlands</aff><aff id="aff7"><label>7</label>Department of Oncology, Hospital La Paz, Madrid, Spain</aff><aff id="aff8"><label>8</label>Department of Dermatology, University of Kiel, Kiel, Germany</aff><aff id="aff9"><label>9</label>Princess Margaret Hospital, Toronto, Canada</aff><aff id="aff10"><label>10</label>Department of Dermatology, Institut Gustave Roussy, Villejuif, France</aff><aff id="aff11"><label>11</label>Department of Dermatology, University Hospital Essen, Essen, Germany</aff><author-notes><corresp id="cor1"><label>*</label><italic>Correspondence to:</italic> Peter Hersey, Room 443, David Maddison Clinical Sciences Building, Corner King and Watt Streets, Newcastle, NSW 2300 Australia; Tel: +61-2-49138828; Fax: +61-2-49138184; Email: <email>Peter.Hersey@newcastle.edu.au</email></corresp></author-notes><pub-date pub-type="epub-ppub"><month>8</month><year>2009</year></pub-date><pmc-comment>Fake ppub date generated by PMC from publisher pub-date/@pub-type='epub-ppub' </pmc-comment>
<pub-date pub-type="ppub"><month>8</month><year>2009</year></pub-date><pub-date pub-type="pmc-release"><month>8</month><year>2009</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>20</volume><issue>Suppl 6</issue><issue-title>Melanoma: Perspectives of the Global Melanoma Task Force</issue-title><fpage>vi35</fpage><lpage>vi40</lpage><permissions><copyright-statement>© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.</copyright-statement><copyright-year>2009</copyright-year><license license-type="open-access"><license-p>The online version of this article has been published under an open access model. users are entitle to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and the European Society for Medical Oncology are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org</license-p></license></permissions><abstract><p>Chemotherapy, biological agents or combinations of both have had little impact on survival of patients with metastatic melanoma. Advances in understanding the genetic changes associated with the development of melanoma resulted in availability of promising new agents that inhibit specific proteins up-regulated in signal cell pathways or inhibit anti-apoptotic proteins. Sorafenib, a multikinase inhibitor of the RAF/RAS/MEK pathway, elesclomol (STA-4783) and oblimersen (G3139), an antisense oligonucleotide targeting anti-apoptotic BCl-2, are in phase III clinical studies in combination with chemotherapy. Agents targeting mutant B-Raf (RAF265 and PLX4032), MEK (PD0325901, AZD6244), heat-shock protein 90 (tanespimycin), mTOR (everolimus, deforolimus, temsirolimus) and VEGFR (axitinib) showed some promise in earlier stages of clinical development. Receptor tyrosine-kinase inhibitors (imatinib, dasatinib, sunitinib) may have a role in treatment of patients with melanoma harbouring c-Kit mutations. Although often studied as single agents with disappointing results, new targeted drugs should be more thoroughly evaluated in combination therapies. The future of rational use of new targeted agents also depends on successful application of analytical techniques enabling molecular profiling of patients and leading to selection of likely therapy responders.</p></abstract><kwd-group><kwd>B-Raf</kwd><kwd>c-Kit</kwd><kwd>inhibitor</kwd><kwd>melanoma</kwd><kwd>mTOR</kwd><kwd>multikinase</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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