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<title xml:lang="en">Biology of Advanced Uveal Melanoma and Next Steps for Clinical Therapeutics</title>
<author>
<name sortKey="Luke, Jason J" sort="Luke, Jason J" uniqKey="Luke J" first="Jason J." last="Luke">Jason J. Luke</name>
<affiliation>
<nlm:aff id="A1">Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave., Boston, MA, 02215 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Triozzi, Pierre L" sort="Triozzi, Pierre L" uniqKey="Triozzi P" first="Pierre L." last="Triozzi">Pierre L. Triozzi</name>
<affiliation>
<nlm:aff id="A2">Wake Forest University Cancer Center, Medical Center Boulevard, Winston-Salem, NC, 27157 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Mckenna, Kyle C" sort="Mckenna, Kyle C" uniqKey="Mckenna K" first="Kyle C." last="Mckenna">Kyle C. Mckenna</name>
<affiliation>
<nlm:aff id="A3">University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Van Meir, Erwin G" sort="Van Meir, Erwin G" uniqKey="Van Meir E" first="Erwin G." last="Van Meir">Erwin G. Van Meir</name>
<affiliation>
<nlm:aff id="A4">School of Medicine and The Winship Cancer Institute of Emory University 1365C Clifton Road, Atlanta, GA, 30322 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Gershenwald, Jeffrey E" sort="Gershenwald, Jeffrey E" uniqKey="Gershenwald J" first="Jeffrey E." last="Gershenwald">Jeffrey E. Gershenwald</name>
<affiliation>
<nlm:aff id="A5">University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Bastian, Boris C" sort="Bastian, Boris C" uniqKey="Bastian B" first="Boris C." last="Bastian">Boris C. Bastian</name>
<affiliation>
<nlm:aff id="A6">University of California San Francisco Helen Diller Comprehensive Cancer Center, 2340 Sutter St., San Francisco, CA, 94115 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Gutkind, J Silvio" sort="Gutkind, J Silvio" uniqKey="Gutkind J" first="J. Silvio" last="Gutkind">J. Silvio Gutkind</name>
<affiliation>
<nlm:aff id="A7">National Institute of Dental and Craniofacial Research, Bethesda, MD 20892-2190 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Bowcock, Anne M" sort="Bowcock, Anne M" uniqKey="Bowcock A" first="Anne M." last="Bowcock">Anne M. Bowcock</name>
<affiliation>
<nlm:aff id="A8">National Heart & Lung Institute, Imperial College, London SW7 2AZ UK</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Streicher, Howard Z" sort="Streicher, Howard Z" uniqKey="Streicher H" first="Howard Z." last="Streicher">Howard Z. Streicher</name>
<affiliation>
<nlm:aff id="A9">National Cancer Institute, Bethesda, MD, 20892 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Patel, Poulam M" sort="Patel, Poulam M" uniqKey="Patel P" first="Poulam M." last="Patel">Poulam M. Patel</name>
<affiliation>
<nlm:aff id="A10">University of Nottingham, Nottingham NG7 2RD, UK</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Sato, Takami" sort="Sato, Takami" uniqKey="Sato T" first="Takami" last="Sato">Takami Sato</name>
<affiliation>
<nlm:aff id="A11">The Kimmel Cancer Center at Jefferson, Thomas Jefferson University, 233 S 10th St Philadelphia, PA, 19107 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Sossman, Jeffery A" sort="Sossman, Jeffery A" uniqKey="Sossman J" first="Jeffery A." last="Sossman">Jeffery A. Sossman</name>
<affiliation>
<nlm:aff id="A12">Vanderbilt-Ingram Cancer Center, Vanderbilt University, 2220 Pierce Ave., Nashville, TN, 37232 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Sznol, Mario" sort="Sznol, Mario" uniqKey="Sznol M" first="Mario" last="Sznol">Mario Sznol</name>
<affiliation>
<nlm:aff id="A13">Yale Cancer Center, Yale University, 20 York St., New Haven, CT, 06510 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Welch, Jack" sort="Welch, Jack" uniqKey="Welch J" first="Jack" last="Welch">Jack Welch</name>
<affiliation>
<nlm:aff id="A9">National Cancer Institute, Bethesda, MD, 20892 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Thurin, Magdalena" sort="Thurin, Magdalena" uniqKey="Thurin M" first="Magdalena" last="Thurin">Magdalena Thurin</name>
<affiliation>
<nlm:aff id="A9">National Cancer Institute, Bethesda, MD, 20892 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Selig, Sara" sort="Selig, Sara" uniqKey="Selig S" first="Sara" last="Selig">Sara Selig</name>
<affiliation>
<nlm:aff id="A14">CURE OM, 1000 H St NW, Washington, DC, 20001 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Flaherty, Keith T" sort="Flaherty, Keith T" uniqKey="Flaherty K" first="Keith T." last="Flaherty">Keith T. Flaherty</name>
<affiliation>
<nlm:aff id="A15">Massachusetts General Hospital Cancer Center, Harvard Medical School, 55 Fruit St, Boston, MA 02114 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Carvajal, Richard D" sort="Carvajal, Richard D" uniqKey="Carvajal R" first="Richard D." last="Carvajal">Richard D. Carvajal</name>
<affiliation>
<nlm:aff id="A16">Memorial-Sloan Kettering Cancer Center, 1275 York Ave., New York, NY, 10065 USA</nlm:aff>
</affiliation>
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<date when="2014">2014</date>
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<title xml:lang="en" level="a" type="main">Biology of Advanced Uveal Melanoma and Next Steps for Clinical Therapeutics</title>
<author>
<name sortKey="Luke, Jason J" sort="Luke, Jason J" uniqKey="Luke J" first="Jason J." last="Luke">Jason J. Luke</name>
<affiliation>
<nlm:aff id="A1">Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave., Boston, MA, 02215 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Triozzi, Pierre L" sort="Triozzi, Pierre L" uniqKey="Triozzi P" first="Pierre L." last="Triozzi">Pierre L. Triozzi</name>
<affiliation>
<nlm:aff id="A2">Wake Forest University Cancer Center, Medical Center Boulevard, Winston-Salem, NC, 27157 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Mckenna, Kyle C" sort="Mckenna, Kyle C" uniqKey="Mckenna K" first="Kyle C." last="Mckenna">Kyle C. Mckenna</name>
<affiliation>
<nlm:aff id="A3">University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Van Meir, Erwin G" sort="Van Meir, Erwin G" uniqKey="Van Meir E" first="Erwin G." last="Van Meir">Erwin G. Van Meir</name>
<affiliation>
<nlm:aff id="A4">School of Medicine and The Winship Cancer Institute of Emory University 1365C Clifton Road, Atlanta, GA, 30322 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Gershenwald, Jeffrey E" sort="Gershenwald, Jeffrey E" uniqKey="Gershenwald J" first="Jeffrey E." last="Gershenwald">Jeffrey E. Gershenwald</name>
<affiliation>
<nlm:aff id="A5">University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Bastian, Boris C" sort="Bastian, Boris C" uniqKey="Bastian B" first="Boris C." last="Bastian">Boris C. Bastian</name>
<affiliation>
<nlm:aff id="A6">University of California San Francisco Helen Diller Comprehensive Cancer Center, 2340 Sutter St., San Francisco, CA, 94115 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Gutkind, J Silvio" sort="Gutkind, J Silvio" uniqKey="Gutkind J" first="J. Silvio" last="Gutkind">J. Silvio Gutkind</name>
<affiliation>
<nlm:aff id="A7">National Institute of Dental and Craniofacial Research, Bethesda, MD 20892-2190 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Bowcock, Anne M" sort="Bowcock, Anne M" uniqKey="Bowcock A" first="Anne M." last="Bowcock">Anne M. Bowcock</name>
<affiliation>
<nlm:aff id="A8">National Heart & Lung Institute, Imperial College, London SW7 2AZ UK</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Streicher, Howard Z" sort="Streicher, Howard Z" uniqKey="Streicher H" first="Howard Z." last="Streicher">Howard Z. Streicher</name>
<affiliation>
<nlm:aff id="A9">National Cancer Institute, Bethesda, MD, 20892 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Patel, Poulam M" sort="Patel, Poulam M" uniqKey="Patel P" first="Poulam M." last="Patel">Poulam M. Patel</name>
<affiliation>
<nlm:aff id="A10">University of Nottingham, Nottingham NG7 2RD, UK</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Sato, Takami" sort="Sato, Takami" uniqKey="Sato T" first="Takami" last="Sato">Takami Sato</name>
<affiliation>
<nlm:aff id="A11">The Kimmel Cancer Center at Jefferson, Thomas Jefferson University, 233 S 10th St Philadelphia, PA, 19107 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Sossman, Jeffery A" sort="Sossman, Jeffery A" uniqKey="Sossman J" first="Jeffery A." last="Sossman">Jeffery A. Sossman</name>
<affiliation>
<nlm:aff id="A12">Vanderbilt-Ingram Cancer Center, Vanderbilt University, 2220 Pierce Ave., Nashville, TN, 37232 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Sznol, Mario" sort="Sznol, Mario" uniqKey="Sznol M" first="Mario" last="Sznol">Mario Sznol</name>
<affiliation>
<nlm:aff id="A13">Yale Cancer Center, Yale University, 20 York St., New Haven, CT, 06510 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Welch, Jack" sort="Welch, Jack" uniqKey="Welch J" first="Jack" last="Welch">Jack Welch</name>
<affiliation>
<nlm:aff id="A9">National Cancer Institute, Bethesda, MD, 20892 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Thurin, Magdalena" sort="Thurin, Magdalena" uniqKey="Thurin M" first="Magdalena" last="Thurin">Magdalena Thurin</name>
<affiliation>
<nlm:aff id="A9">National Cancer Institute, Bethesda, MD, 20892 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Selig, Sara" sort="Selig, Sara" uniqKey="Selig S" first="Sara" last="Selig">Sara Selig</name>
<affiliation>
<nlm:aff id="A14">CURE OM, 1000 H St NW, Washington, DC, 20001 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Flaherty, Keith T" sort="Flaherty, Keith T" uniqKey="Flaherty K" first="Keith T." last="Flaherty">Keith T. Flaherty</name>
<affiliation>
<nlm:aff id="A15">Massachusetts General Hospital Cancer Center, Harvard Medical School, 55 Fruit St, Boston, MA 02114 USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Carvajal, Richard D" sort="Carvajal, Richard D" uniqKey="Carvajal R" first="Richard D." last="Carvajal">Richard D. Carvajal</name>
<affiliation>
<nlm:aff id="A16">Memorial-Sloan Kettering Cancer Center, 1275 York Ave., New York, NY, 10065 USA</nlm:aff>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Pigment cell & melanoma research</title>
<idno type="ISSN">1755-1471</idno>
<idno type="eISSN">1755-148X</idno>
<imprint>
<date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
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<textClass></textClass>
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<front>
<div type="abstract" xml:lang="en">
<title>Summary</title>
<p id="P1">Uveal melanoma is the most common intraocular malignancy though it is a rare subset of all melanomas. Uveal melanoma has distinct biology relative to cutaneous melanoma, with widely divergent patient outcomes. Patients diagnosed with a primary uveal melanoma can be stratified for risk of metastasis by cytogenetics or gene expression profiling, with approximately half of patients developing metastatic disease, predominately hepatic in location, over a 15 year period. Historically, no systemic therapy has been associated with a clear clinical benefit for patients with advanced disease and median survival remains poor. Here, as a joint effort between CURE OM and the National Cancer Institute, the current understanding of the molecular and immunobiology of uveal melanoma is reviewed, and on-going laboratory research into the disease is highlighted. Finally, recent investigations relevant to clinical management via targeted and immunotherpies are reviewed and next steps in the development of clinical therapeutics are discussed.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-journal-id">101318927</journal-id>
<journal-id journal-id-type="pubmed-jr-id">34207</journal-id>
<journal-id journal-id-type="nlm-ta">Pigment Cell Melanoma Res</journal-id>
<journal-id journal-id-type="iso-abbrev">Pigment Cell Melanoma Res</journal-id>
<journal-title-group>
<journal-title>Pigment cell & melanoma research</journal-title>
</journal-title-group>
<issn pub-type="ppub">1755-1471</issn>
<issn pub-type="epub">1755-148X</issn>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">25113308</article-id>
<article-id pub-id-type="pmc">4326637</article-id>
<article-id pub-id-type="doi">10.1111/pcmr.12304</article-id>
<article-id pub-id-type="manuscript">NIHMS621657</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Biology of Advanced Uveal Melanoma and Next Steps for Clinical Therapeutics</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Luke</surname>
<given-names>Jason J.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Triozzi</surname>
<given-names>Pierre L.</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>McKenna</surname>
<given-names>Kyle C.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Van Meir</surname>
<given-names>Erwin G.</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gershenwald</surname>
<given-names>Jeffrey E.</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bastian</surname>
<given-names>Boris C.</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gutkind</surname>
<given-names>J. Silvio</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bowcock</surname>
<given-names>Anne M.</given-names>
</name>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Streicher</surname>
<given-names>Howard Z.</given-names>
</name>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Patel</surname>
<given-names>Poulam M.</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sato</surname>
<given-names>Takami</given-names>
</name>
<xref ref-type="aff" rid="A11">11</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sossman</surname>
<given-names>Jeffery A.</given-names>
</name>
<xref ref-type="aff" rid="A12">12</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sznol</surname>
<given-names>Mario</given-names>
</name>
<xref ref-type="aff" rid="A13">13</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Welch</surname>
<given-names>Jack</given-names>
</name>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Thurin</surname>
<given-names>Magdalena</given-names>
</name>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Selig</surname>
<given-names>Sara</given-names>
</name>
<xref ref-type="aff" rid="A14">14</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Flaherty</surname>
<given-names>Keith T.</given-names>
</name>
<xref ref-type="aff" rid="A15">15</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Carvajal</surname>
<given-names>Richard D.</given-names>
</name>
<xref ref-type="aff" rid="A16">16</xref>
</contrib>
</contrib-group>
<aff id="A1">
<label>1</label>
Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave., Boston, MA, 02215 USA</aff>
<aff id="A2">
<label>2</label>
Wake Forest University Cancer Center, Medical Center Boulevard, Winston-Salem, NC, 27157 USA</aff>
<aff id="A3">
<label>3</label>
University of Pittsburgh Cancer Institute, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA</aff>
<aff id="A4">
<label>4</label>
School of Medicine and The Winship Cancer Institute of Emory University 1365C Clifton Road, Atlanta, GA, 30322 USA</aff>
<aff id="A5">
<label>5</label>
University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030 USA</aff>
<aff id="A6">
<label>6</label>
University of California San Francisco Helen Diller Comprehensive Cancer Center, 2340 Sutter St., San Francisco, CA, 94115 USA</aff>
<aff id="A7">
<label>7</label>
National Institute of Dental and Craniofacial Research, Bethesda, MD 20892-2190 USA</aff>
<aff id="A8">
<label>8</label>
National Heart & Lung Institute, Imperial College, London SW7 2AZ UK</aff>
<aff id="A9">
<label>9</label>
National Cancer Institute, Bethesda, MD, 20892 USA</aff>
<aff id="A10">
<label>10</label>
University of Nottingham, Nottingham NG7 2RD, UK</aff>
<aff id="A11">
<label>11</label>
The Kimmel Cancer Center at Jefferson, Thomas Jefferson University, 233 S 10th St Philadelphia, PA, 19107 USA</aff>
<aff id="A12">
<label>12</label>
Vanderbilt-Ingram Cancer Center, Vanderbilt University, 2220 Pierce Ave., Nashville, TN, 37232 USA</aff>
<aff id="A13">
<label>13</label>
Yale Cancer Center, Yale University, 20 York St., New Haven, CT, 06510 USA</aff>
<aff id="A14">
<label>14</label>
CURE OM, 1000 H St NW, Washington, DC, 20001 USA</aff>
<aff id="A15">
<label>15</label>
Massachusetts General Hospital Cancer Center, Harvard Medical School, 55 Fruit St, Boston, MA 02114 USA</aff>
<aff id="A16">
<label>16</label>
Memorial-Sloan Kettering Cancer Center, 1275 York Ave., New York, NY, 10065 USA</aff>
<author-notes>
<corresp id="FN1">
<label>*</label>
Corresponding Author: Jason J. Luke, Melanoma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave., Boston, MA 02215, Ph: 6176324715, Fax: 6176326727,
<email>Jason_Luke@dfci.harvard.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted">
<day>20</day>
<month>8</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub">
<day>01</day>
<month>9</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="ppub">
<month>3</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>01</day>
<month>3</month>
<year>2016</year>
</pub-date>
<volume>28</volume>
<issue>2</issue>
<fpage>135</fpage>
<lpage>147</lpage>
<pmc-comment>elocation-id from pubmed: 10.1111/pcmr.12304</pmc-comment>
<abstract>
<title>Summary</title>
<p id="P1">Uveal melanoma is the most common intraocular malignancy though it is a rare subset of all melanomas. Uveal melanoma has distinct biology relative to cutaneous melanoma, with widely divergent patient outcomes. Patients diagnosed with a primary uveal melanoma can be stratified for risk of metastasis by cytogenetics or gene expression profiling, with approximately half of patients developing metastatic disease, predominately hepatic in location, over a 15 year period. Historically, no systemic therapy has been associated with a clear clinical benefit for patients with advanced disease and median survival remains poor. Here, as a joint effort between CURE OM and the National Cancer Institute, the current understanding of the molecular and immunobiology of uveal melanoma is reviewed, and on-going laboratory research into the disease is highlighted. Finally, recent investigations relevant to clinical management via targeted and immunotherpies are reviewed and next steps in the development of clinical therapeutics are discussed.</p>
</abstract>
<kwd-group>
<kwd>Ocular</kwd>
<kwd>Uveal</kwd>
<kwd>Melanoma</kwd>
<kwd>MEK</kwd>
<kwd>GNAQ</kwd>
<kwd>GNA11</kwd>
<kwd>metastasis</kwd>
<kwd>cancer</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>

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