Targeting HER2-positive breast cancer: advances and future directions
The long-sought discovery of HER2 as an actionable and highly sensitive therapeutic target was a major breakthrough for the treatment of highly aggressive HER2-positive breast cancer, leading to approval of the first HER2-targeted drug — the monoclonal antibody trastuzumab — almost 25 years ago. Sin...
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| Veröffentlicht in: | Nature reviews. Drug discovery 2023-02, Vol.22 (2), p.101-126 |
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| creator | Swain, Sandra M. Shastry, Mythili Hamilton, Erika |
| description | The long-sought discovery of HER2 as an actionable and highly sensitive therapeutic target was a major breakthrough for the treatment of highly aggressive HER2-positive breast cancer, leading to approval of the first HER2-targeted drug — the monoclonal antibody trastuzumab — almost 25 years ago. Since then, progress has been swift and the impressive clinical activity across multiple trials with monoclonal antibodies, tyrosine kinase inhibitors and antibody–drug conjugates that target HER2 has spawned extensive efforts to develop newer platforms and more targeted therapies. This Review discusses the current standards of care for HER2-positive breast cancer, mechanisms of resistance to HER2-targeted therapy and new therapeutic approaches and agents, including strategies to harness the immune system.
The discovery of the monoclonal antibody trastuzumab almost 25 years ago revolutionized treatment and drug development for HER2
+
breast cancer. Here, Swain et al. review the current standard of care for HER2
+
breast cancer, describe mechanisms of drug resistance and focus on next-generation platforms and therapies for the treatment of this disease. |
| doi_str_mv | 10.1038/s41573-022-00579-0 |
| format | Article |
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The discovery of the monoclonal antibody trastuzumab almost 25 years ago revolutionized treatment and drug development for HER2
+
breast cancer. Here, Swain et al. review the current standard of care for HER2
+
breast cancer, describe mechanisms of drug resistance and focus on next-generation platforms and therapies for the treatment of this disease.</description><identifier>ISSN: 1474-1776</identifier><identifier>ISSN: 1474-1784</identifier><identifier>EISSN: 1474-1784</identifier><identifier>DOI: 10.1038/s41573-022-00579-0</identifier><identifier>PMID: 36344672</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/1347 ; 692/4028/67/1347 ; Antibodies, Monoclonal - pharmacology ; Antibodies, Monoclonal - therapeutic use ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Biomedical and Life Sciences ; Biomedicine ; Biotechnology ; Breast cancer ; Breast Neoplasms - drug therapy ; Cancer Research ; Cancer therapies ; Chromosomes ; Drug development ; Epidermal growth factor ; Female ; Gene amplification ; Humans ; Immune system ; Immunotherapy ; Kinases ; Medicinal Chemistry ; Medicine ; Metastasis ; Molecular Medicine ; Monoclonal antibodies ; Nobel prizes ; Pharmacology/Toxicology ; Physiology ; Proteins ; R&D ; Receptor, ErbB-2 ; Research & development ; Review ; Review Article ; Trastuzumab - pharmacology ; Trastuzumab - therapeutic use ; Tumors</subject><ispartof>Nature reviews. Drug discovery, 2023-02, Vol.22 (2), p.101-126</ispartof><rights>Springer Nature Limited 2022 Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2022. Springer Nature Limited.</rights><rights>Copyright Nature Publishing Group Feb 2023</rights><rights>Springer Nature Limited 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-cff1cbb8618b6e0157444b016f8bee602e7343fb9c0333646754acda596d6f403</citedby><cites>FETCH-LOGICAL-c540t-cff1cbb8618b6e0157444b016f8bee602e7343fb9c0333646754acda596d6f403</cites><orcidid>0000-0003-2445-8094 ; 0000-0002-1911-0336 ; 0000-0002-1320-3830</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41573-022-00579-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41573-022-00579-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36344672$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Swain, Sandra M.</creatorcontrib><creatorcontrib>Shastry, Mythili</creatorcontrib><creatorcontrib>Hamilton, Erika</creatorcontrib><title>Targeting HER2-positive breast cancer: advances and future directions</title><title>Nature reviews. Drug discovery</title><addtitle>Nat Rev Drug Discov</addtitle><addtitle>Nat Rev Drug Discov</addtitle><description>The long-sought discovery of HER2 as an actionable and highly sensitive therapeutic target was a major breakthrough for the treatment of highly aggressive HER2-positive breast cancer, leading to approval of the first HER2-targeted drug — the monoclonal antibody trastuzumab — almost 25 years ago. Since then, progress has been swift and the impressive clinical activity across multiple trials with monoclonal antibodies, tyrosine kinase inhibitors and antibody–drug conjugates that target HER2 has spawned extensive efforts to develop newer platforms and more targeted therapies. This Review discusses the current standards of care for HER2-positive breast cancer, mechanisms of resistance to HER2-targeted therapy and new therapeutic approaches and agents, including strategies to harness the immune system.
The discovery of the monoclonal antibody trastuzumab almost 25 years ago revolutionized treatment and drug development for HER2
+
breast cancer. Here, Swain et al. review the current standard of care for HER2
+
breast cancer, describe mechanisms of drug resistance and focus on next-generation platforms and therapies for the treatment of this disease.</description><subject>631/67/1347</subject><subject>692/4028/67/1347</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Cancer Research</subject><subject>Cancer therapies</subject><subject>Chromosomes</subject><subject>Drug development</subject><subject>Epidermal growth factor</subject><subject>Female</subject><subject>Gene amplification</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immunotherapy</subject><subject>Kinases</subject><subject>Medicinal Chemistry</subject><subject>Medicine</subject><subject>Metastasis</subject><subject>Molecular Medicine</subject><subject>Monoclonal antibodies</subject><subject>Nobel prizes</subject><subject>Pharmacology/Toxicology</subject><subject>Physiology</subject><subject>Proteins</subject><subject>R&D</subject><subject>Receptor, ErbB-2</subject><subject>Research & development</subject><subject>Review</subject><subject>Review Article</subject><subject>Trastuzumab - pharmacology</subject><subject>Trastuzumab - therapeutic use</subject><subject>Tumors</subject><issn>1474-1776</issn><issn>1474-1784</issn><issn>1474-1784</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kUtLAzEUhYMotlb_gAsZcONmNK9JZlwIUuoDCoLUdchk7tSUNlOTmYL_3tTW-li4yoX75eScHIROCb4kmOVXgZNMshRTmmKcySLFe6hPuOQpkTnf381S9NBRCDOMiSCSHqIeE4xzIWkfjSbaT6G1bpo8jJ5pumyCbe0KktKDDm1itDPgrxNdrdZTSLSrkrprOw9JZT2Y1jYuHKODWs8DnGzPAXq5G02GD-n46f5xeDtOTcZxm5q6JqYsc0HyUgCO7jnnZXRV5yWAwBQk46wuC4MZYyI6zLg2lc4KUYmaYzZANxvdZVcuoDLgWq_nauntQvt31Wirfm-cfVXTZqUKwXH8kyhwsRXwzVsHoVULGwzM59pB0wVFowEiBKdFRM__oLOm8y7Gi5SkpBAFzSJFN5TxTQge6p0ZgtW6JbVpScWW1GdLah3j7GeM3ZWvWiLANkCIKzcF__32P7IfqXadCg</recordid><startdate>20230201</startdate><enddate>20230201</enddate><creator>Swain, Sandra M.</creator><creator>Shastry, Mythili</creator><creator>Hamilton, Erika</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><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>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2445-8094</orcidid><orcidid>https://orcid.org/0000-0002-1911-0336</orcidid><orcidid>https://orcid.org/0000-0002-1320-3830</orcidid></search><sort><creationdate>20230201</creationdate><title>Targeting HER2-positive breast cancer: advances and future directions</title><author>Swain, Sandra M. ; Shastry, Mythili ; Hamilton, Erika</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-cff1cbb8618b6e0157444b016f8bee602e7343fb9c0333646754acda596d6f403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>631/67/1347</topic><topic>692/4028/67/1347</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Cancer Research</topic><topic>Cancer therapies</topic><topic>Chromosomes</topic><topic>Drug development</topic><topic>Epidermal growth factor</topic><topic>Female</topic><topic>Gene amplification</topic><topic>Humans</topic><topic>Immune system</topic><topic>Immunotherapy</topic><topic>Kinases</topic><topic>Medicinal Chemistry</topic><topic>Medicine</topic><topic>Metastasis</topic><topic>Molecular Medicine</topic><topic>Monoclonal antibodies</topic><topic>Nobel prizes</topic><topic>Pharmacology/Toxicology</topic><topic>Physiology</topic><topic>Proteins</topic><topic>R&D</topic><topic>Receptor, ErbB-2</topic><topic>Research & development</topic><topic>Review</topic><topic>Review Article</topic><topic>Trastuzumab - pharmacology</topic><topic>Trastuzumab - therapeutic use</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Swain, Sandra M.</creatorcontrib><creatorcontrib>Shastry, Mythili</creatorcontrib><creatorcontrib>Hamilton, Erika</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature reviews. Drug discovery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Swain, Sandra M.</au><au>Shastry, Mythili</au><au>Hamilton, Erika</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeting HER2-positive breast cancer: advances and future directions</atitle><jtitle>Nature reviews. Drug discovery</jtitle><stitle>Nat Rev Drug Discov</stitle><addtitle>Nat Rev Drug Discov</addtitle><date>2023-02-01</date><risdate>2023</risdate><volume>22</volume><issue>2</issue><spage>101</spage><epage>126</epage><pages>101-126</pages><issn>1474-1776</issn><issn>1474-1784</issn><eissn>1474-1784</eissn><abstract>The long-sought discovery of HER2 as an actionable and highly sensitive therapeutic target was a major breakthrough for the treatment of highly aggressive HER2-positive breast cancer, leading to approval of the first HER2-targeted drug — the monoclonal antibody trastuzumab — almost 25 years ago. Since then, progress has been swift and the impressive clinical activity across multiple trials with monoclonal antibodies, tyrosine kinase inhibitors and antibody–drug conjugates that target HER2 has spawned extensive efforts to develop newer platforms and more targeted therapies. This Review discusses the current standards of care for HER2-positive breast cancer, mechanisms of resistance to HER2-targeted therapy and new therapeutic approaches and agents, including strategies to harness the immune system.
The discovery of the monoclonal antibody trastuzumab almost 25 years ago revolutionized treatment and drug development for HER2
+
breast cancer. Here, Swain et al. review the current standard of care for HER2
+
breast cancer, describe mechanisms of drug resistance and focus on next-generation platforms and therapies for the treatment of this disease.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>36344672</pmid><doi>10.1038/s41573-022-00579-0</doi><tpages>26</tpages><orcidid>https://orcid.org/0000-0003-2445-8094</orcidid><orcidid>https://orcid.org/0000-0002-1911-0336</orcidid><orcidid>https://orcid.org/0000-0002-1320-3830</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 631/67/1347 692/4028/67/1347 Antibodies, Monoclonal - pharmacology Antibodies, Monoclonal - therapeutic use Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Biomedical and Life Sciences Biomedicine Biotechnology Breast cancer Breast Neoplasms - drug therapy Cancer Research Cancer therapies Chromosomes Drug development Epidermal growth factor Female Gene amplification Humans Immune system Immunotherapy Kinases Medicinal Chemistry Medicine Metastasis Molecular Medicine Monoclonal antibodies Nobel prizes Pharmacology/Toxicology Physiology Proteins R&D Receptor, ErbB-2 Research & development Review Review Article Trastuzumab - pharmacology Trastuzumab - therapeutic use Tumors |
| title | Targeting HER2-positive breast cancer: advances and future directions |
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