Activation of the IFN Signaling Pathway is Associated with Resistance to CDK4/6 Inhibitors and Immune Checkpoint Activation in ER-Positive Breast Cancer
Cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (CDK4/6i) are highly effective against estrogen receptor-positive (ER )/HER2 breast cancer; however, intrinsic and acquired resistance is common. Elucidating the molecular features of sensitivity and resistance to CDK4/6i may lead to identificatio...
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| Veröffentlicht in: | Clinical cancer research 2021-09, Vol.27 (17), p.4870-4882 |
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| creator | De Angelis, Carmine Fu, Xiaoyong Cataldo, Maria Letizia Nardone, Agostina Pereira, Resel Veeraraghavan, Jamunarani Nanda, Sarmistha Qin, Lanfang Sethunath, Vidyalakshmi Wang, Tao Hilsenbeck, Susan G Benelli, Matteo Migliaccio, Ilenia Guarducci, Cristina Malorni, Luca Litchfield, Lacey M Liu, Jiangang Donaldson, Joshua Selenica, Pier Brown, David N Weigelt, Britta Reis-Filho, Jorge S Park, Ben H Hurvitz, Sara A Slamon, Dennis J Rimawi, Mothaffar F Jansen, Valerie M Jeselsohn, Rinath Osborne, C Kent Schiff, Rachel |
| description | Cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (CDK4/6i) are highly effective against estrogen receptor-positive (ER
)/HER2
breast cancer; however, intrinsic and acquired resistance is common. Elucidating the molecular features of sensitivity and resistance to CDK4/6i may lead to identification of predictive biomarkers and novel therapeutic targets, paving the way toward improving patient outcomes.
Parental breast cancer cells and their endocrine-resistant derivatives (EndoR) were used. Derivatives with acquired resistance to palbociclib (PalboR) were generated from parental and estrogen deprivation-resistant MCF7 and T47D cells. Transcriptomic and proteomic analyses were performed in palbociclib-sensitive and PalboR lines. Gene expression data from CDK4/6i neoadjuvant trials and publicly available datasets were interrogated for correlations of gene signatures and patient outcomes.
Parental and EndoR breast cancer lines showed varying degrees of sensitivity to palbociclib. Transcriptomic analysis of these cell lines identified an association between high IFN signaling and reduced CDK4/6i sensitivity; thus an "IFN-related palbociclib-resistance Signature" (IRPS) was derived. In two neoadjuvant trials of CDK4/6i plus endocrine therapy, IRPS and other IFN-related signatures were highly enriched in patients with tumors exhibiting intrinsic resistance to CDK4/6i. PalboR derivatives displayed dramatic activation of IFN/STAT1 signaling compared with their short-term treated or untreated counterparts. In primary ER
/HER2
tumors, the IRPS score was significantly higher in lumB than lumA subtype and correlated with increased gene expression of immune checkpoints, endocrine resistance, and poor prognosis.
Aberrant IFN signaling is associated with intrinsic resistance to CDK4/6i. Experimentally, acquired resistance to palbociclib is associated with activation of the IFN pathway, warranting additional studies to clarify its involvement in resistance to CDK4/6i. |
| doi_str_mv | 10.1158/1078-0432.CCR-19-4191 |
| format | Article |
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)/HER2
breast cancer; however, intrinsic and acquired resistance is common. Elucidating the molecular features of sensitivity and resistance to CDK4/6i may lead to identification of predictive biomarkers and novel therapeutic targets, paving the way toward improving patient outcomes.
Parental breast cancer cells and their endocrine-resistant derivatives (EndoR) were used. Derivatives with acquired resistance to palbociclib (PalboR) were generated from parental and estrogen deprivation-resistant MCF7 and T47D cells. Transcriptomic and proteomic analyses were performed in palbociclib-sensitive and PalboR lines. Gene expression data from CDK4/6i neoadjuvant trials and publicly available datasets were interrogated for correlations of gene signatures and patient outcomes.
Parental and EndoR breast cancer lines showed varying degrees of sensitivity to palbociclib. Transcriptomic analysis of these cell lines identified an association between high IFN signaling and reduced CDK4/6i sensitivity; thus an "IFN-related palbociclib-resistance Signature" (IRPS) was derived. In two neoadjuvant trials of CDK4/6i plus endocrine therapy, IRPS and other IFN-related signatures were highly enriched in patients with tumors exhibiting intrinsic resistance to CDK4/6i. PalboR derivatives displayed dramatic activation of IFN/STAT1 signaling compared with their short-term treated or untreated counterparts. In primary ER
/HER2
tumors, the IRPS score was significantly higher in lumB than lumA subtype and correlated with increased gene expression of immune checkpoints, endocrine resistance, and poor prognosis.
Aberrant IFN signaling is associated with intrinsic resistance to CDK4/6i. Experimentally, acquired resistance to palbociclib is associated with activation of the IFN pathway, warranting additional studies to clarify its involvement in resistance to CDK4/6i.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-19-4191</identifier><identifier>PMID: 33536276</identifier><language>eng</language><publisher>United States</publisher><subject>Antineoplastic Agents - therapeutic use ; Breast Neoplasms - chemistry ; Breast Neoplasms - drug therapy ; Cyclin-Dependent Kinase 4 - antagonists & inhibitors ; Cyclin-Dependent Kinase 6 - antagonists & inhibitors ; Female ; Humans ; Piperazines - therapeutic use ; Pyridines - therapeutic use ; Receptors, Estrogen - analysis ; Signal Transduction ; Tumor Cells, Cultured</subject><ispartof>Clinical cancer research, 2021-09, Vol.27 (17), p.4870-4882</ispartof><rights>2021 American Association for Cancer Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-2009bb79c924b16a28c1c0feeaf4460f8736571cf01c70b7bb8f559ae9e5ce393</citedby><cites>FETCH-LOGICAL-c356t-2009bb79c924b16a28c1c0feeaf4460f8736571cf01c70b7bb8f559ae9e5ce393</cites><orcidid>0000-0002-7962-673X ; 0000-0003-1957-7160 ; 0000-0003-1227-356X ; 0000-0003-0005-6496 ; 0000-0002-4297-2997 ; 0000-0002-2800-077X ; 0000-0003-1696-5213 ; 0000-0001-7996-7529</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3343,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33536276$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>De Angelis, Carmine</creatorcontrib><creatorcontrib>Fu, Xiaoyong</creatorcontrib><creatorcontrib>Cataldo, Maria Letizia</creatorcontrib><creatorcontrib>Nardone, Agostina</creatorcontrib><creatorcontrib>Pereira, Resel</creatorcontrib><creatorcontrib>Veeraraghavan, Jamunarani</creatorcontrib><creatorcontrib>Nanda, Sarmistha</creatorcontrib><creatorcontrib>Qin, Lanfang</creatorcontrib><creatorcontrib>Sethunath, Vidyalakshmi</creatorcontrib><creatorcontrib>Wang, Tao</creatorcontrib><creatorcontrib>Hilsenbeck, Susan G</creatorcontrib><creatorcontrib>Benelli, Matteo</creatorcontrib><creatorcontrib>Migliaccio, Ilenia</creatorcontrib><creatorcontrib>Guarducci, Cristina</creatorcontrib><creatorcontrib>Malorni, Luca</creatorcontrib><creatorcontrib>Litchfield, Lacey M</creatorcontrib><creatorcontrib>Liu, Jiangang</creatorcontrib><creatorcontrib>Donaldson, Joshua</creatorcontrib><creatorcontrib>Selenica, Pier</creatorcontrib><creatorcontrib>Brown, David N</creatorcontrib><creatorcontrib>Weigelt, Britta</creatorcontrib><creatorcontrib>Reis-Filho, Jorge S</creatorcontrib><creatorcontrib>Park, Ben H</creatorcontrib><creatorcontrib>Hurvitz, Sara A</creatorcontrib><creatorcontrib>Slamon, Dennis J</creatorcontrib><creatorcontrib>Rimawi, Mothaffar F</creatorcontrib><creatorcontrib>Jansen, Valerie M</creatorcontrib><creatorcontrib>Jeselsohn, Rinath</creatorcontrib><creatorcontrib>Osborne, C Kent</creatorcontrib><creatorcontrib>Schiff, Rachel</creatorcontrib><title>Activation of the IFN Signaling Pathway is Associated with Resistance to CDK4/6 Inhibitors and Immune Checkpoint Activation in ER-Positive Breast Cancer</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (CDK4/6i) are highly effective against estrogen receptor-positive (ER
)/HER2
breast cancer; however, intrinsic and acquired resistance is common. Elucidating the molecular features of sensitivity and resistance to CDK4/6i may lead to identification of predictive biomarkers and novel therapeutic targets, paving the way toward improving patient outcomes.
Parental breast cancer cells and their endocrine-resistant derivatives (EndoR) were used. Derivatives with acquired resistance to palbociclib (PalboR) were generated from parental and estrogen deprivation-resistant MCF7 and T47D cells. Transcriptomic and proteomic analyses were performed in palbociclib-sensitive and PalboR lines. Gene expression data from CDK4/6i neoadjuvant trials and publicly available datasets were interrogated for correlations of gene signatures and patient outcomes.
Parental and EndoR breast cancer lines showed varying degrees of sensitivity to palbociclib. Transcriptomic analysis of these cell lines identified an association between high IFN signaling and reduced CDK4/6i sensitivity; thus an "IFN-related palbociclib-resistance Signature" (IRPS) was derived. In two neoadjuvant trials of CDK4/6i plus endocrine therapy, IRPS and other IFN-related signatures were highly enriched in patients with tumors exhibiting intrinsic resistance to CDK4/6i. PalboR derivatives displayed dramatic activation of IFN/STAT1 signaling compared with their short-term treated or untreated counterparts. In primary ER
/HER2
tumors, the IRPS score was significantly higher in lumB than lumA subtype and correlated with increased gene expression of immune checkpoints, endocrine resistance, and poor prognosis.
Aberrant IFN signaling is associated with intrinsic resistance to CDK4/6i. Experimentally, acquired resistance to palbociclib is associated with activation of the IFN pathway, warranting additional studies to clarify its involvement in resistance to CDK4/6i.</description><subject>Antineoplastic Agents - therapeutic use</subject><subject>Breast Neoplasms - chemistry</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Cyclin-Dependent Kinase 4 - antagonists & inhibitors</subject><subject>Cyclin-Dependent Kinase 6 - antagonists & inhibitors</subject><subject>Female</subject><subject>Humans</subject><subject>Piperazines - therapeutic use</subject><subject>Pyridines - therapeutic use</subject><subject>Receptors, Estrogen - analysis</subject><subject>Signal Transduction</subject><subject>Tumor Cells, Cultured</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkd1O3DAQhS3Uir_2EUBz2ZuAHf8kvtym0K6KWrTQa8vxTohhY29jbxFv0sclEVD1akajc85I5yPkhNEzxmR9zmhVF1Tw8qxpVgXThWCa7ZFDJmVV8FLJd9P-pjkgRyndU8oEo2KfHHAuuSordUj-Llz2f2z2MUDsIPcIy8sfcOPvgt34cAfXNveP9gl8gkVK0XmbcQ2PPvewwuRTtsEh5AjNl-_iXMEy9L71OY4JbFjDchh2AaHp0T1sow8Z_nvoA1ysiuuY_HRC-DyiTRmaOXH8QN53dpPw4-s8Jr8uL26bb8XVz6_LZnFVOC5VLkpKddtW2ulStEzZsnbM0Q7RdkIo2tUVV7JirqPMVbSt2rbupNQWNUqHXPNj8ukldzvG3ztM2Qw-OdxsbMC4S6YUtRKqZLqepPJF6saY0oid2Y5-sOOTYdTMUMxcuJkLNxMUw7SZoUy-09cXu3bA9T_XGwX-DLhfiPI</recordid><startdate>20210901</startdate><enddate>20210901</enddate><creator>De Angelis, Carmine</creator><creator>Fu, Xiaoyong</creator><creator>Cataldo, Maria Letizia</creator><creator>Nardone, Agostina</creator><creator>Pereira, Resel</creator><creator>Veeraraghavan, Jamunarani</creator><creator>Nanda, Sarmistha</creator><creator>Qin, Lanfang</creator><creator>Sethunath, Vidyalakshmi</creator><creator>Wang, Tao</creator><creator>Hilsenbeck, Susan G</creator><creator>Benelli, Matteo</creator><creator>Migliaccio, Ilenia</creator><creator>Guarducci, Cristina</creator><creator>Malorni, Luca</creator><creator>Litchfield, Lacey M</creator><creator>Liu, Jiangang</creator><creator>Donaldson, Joshua</creator><creator>Selenica, Pier</creator><creator>Brown, David N</creator><creator>Weigelt, Britta</creator><creator>Reis-Filho, Jorge S</creator><creator>Park, Ben H</creator><creator>Hurvitz, Sara A</creator><creator>Slamon, Dennis J</creator><creator>Rimawi, Mothaffar F</creator><creator>Jansen, Valerie M</creator><creator>Jeselsohn, Rinath</creator><creator>Osborne, C Kent</creator><creator>Schiff, Rachel</creator><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>7X8</scope><orcidid>https://orcid.org/0000-0002-7962-673X</orcidid><orcidid>https://orcid.org/0000-0003-1957-7160</orcidid><orcidid>https://orcid.org/0000-0003-1227-356X</orcidid><orcidid>https://orcid.org/0000-0003-0005-6496</orcidid><orcidid>https://orcid.org/0000-0002-4297-2997</orcidid><orcidid>https://orcid.org/0000-0002-2800-077X</orcidid><orcidid>https://orcid.org/0000-0003-1696-5213</orcidid><orcidid>https://orcid.org/0000-0001-7996-7529</orcidid></search><sort><creationdate>20210901</creationdate><title>Activation of the IFN Signaling Pathway is Associated with Resistance to CDK4/6 Inhibitors and Immune Checkpoint Activation in ER-Positive Breast Cancer</title><author>De Angelis, Carmine ; Fu, Xiaoyong ; Cataldo, Maria Letizia ; Nardone, Agostina ; Pereira, Resel ; Veeraraghavan, Jamunarani ; Nanda, Sarmistha ; Qin, Lanfang ; Sethunath, Vidyalakshmi ; Wang, Tao ; Hilsenbeck, Susan G ; Benelli, Matteo ; Migliaccio, Ilenia ; Guarducci, Cristina ; Malorni, Luca ; Litchfield, Lacey M ; Liu, Jiangang ; Donaldson, Joshua ; Selenica, Pier ; Brown, David N ; Weigelt, Britta ; Reis-Filho, Jorge S ; Park, Ben H ; Hurvitz, Sara A ; Slamon, Dennis J ; Rimawi, Mothaffar F ; Jansen, Valerie M ; Jeselsohn, Rinath ; Osborne, C Kent ; Schiff, Rachel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-2009bb79c924b16a28c1c0feeaf4460f8736571cf01c70b7bb8f559ae9e5ce393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antineoplastic Agents - therapeutic use</topic><topic>Breast Neoplasms - chemistry</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Cyclin-Dependent Kinase 4 - antagonists & inhibitors</topic><topic>Cyclin-Dependent Kinase 6 - antagonists & inhibitors</topic><topic>Female</topic><topic>Humans</topic><topic>Piperazines - therapeutic use</topic><topic>Pyridines - therapeutic use</topic><topic>Receptors, Estrogen - analysis</topic><topic>Signal Transduction</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>De Angelis, Carmine</creatorcontrib><creatorcontrib>Fu, Xiaoyong</creatorcontrib><creatorcontrib>Cataldo, Maria Letizia</creatorcontrib><creatorcontrib>Nardone, Agostina</creatorcontrib><creatorcontrib>Pereira, Resel</creatorcontrib><creatorcontrib>Veeraraghavan, Jamunarani</creatorcontrib><creatorcontrib>Nanda, Sarmistha</creatorcontrib><creatorcontrib>Qin, Lanfang</creatorcontrib><creatorcontrib>Sethunath, Vidyalakshmi</creatorcontrib><creatorcontrib>Wang, Tao</creatorcontrib><creatorcontrib>Hilsenbeck, Susan G</creatorcontrib><creatorcontrib>Benelli, Matteo</creatorcontrib><creatorcontrib>Migliaccio, Ilenia</creatorcontrib><creatorcontrib>Guarducci, Cristina</creatorcontrib><creatorcontrib>Malorni, Luca</creatorcontrib><creatorcontrib>Litchfield, Lacey M</creatorcontrib><creatorcontrib>Liu, Jiangang</creatorcontrib><creatorcontrib>Donaldson, Joshua</creatorcontrib><creatorcontrib>Selenica, Pier</creatorcontrib><creatorcontrib>Brown, David N</creatorcontrib><creatorcontrib>Weigelt, Britta</creatorcontrib><creatorcontrib>Reis-Filho, Jorge S</creatorcontrib><creatorcontrib>Park, Ben H</creatorcontrib><creatorcontrib>Hurvitz, Sara A</creatorcontrib><creatorcontrib>Slamon, Dennis J</creatorcontrib><creatorcontrib>Rimawi, Mothaffar F</creatorcontrib><creatorcontrib>Jansen, Valerie M</creatorcontrib><creatorcontrib>Jeselsohn, Rinath</creatorcontrib><creatorcontrib>Osborne, C Kent</creatorcontrib><creatorcontrib>Schiff, Rachel</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>De Angelis, Carmine</au><au>Fu, Xiaoyong</au><au>Cataldo, Maria Letizia</au><au>Nardone, Agostina</au><au>Pereira, Resel</au><au>Veeraraghavan, Jamunarani</au><au>Nanda, Sarmistha</au><au>Qin, Lanfang</au><au>Sethunath, Vidyalakshmi</au><au>Wang, Tao</au><au>Hilsenbeck, Susan G</au><au>Benelli, Matteo</au><au>Migliaccio, Ilenia</au><au>Guarducci, Cristina</au><au>Malorni, Luca</au><au>Litchfield, Lacey M</au><au>Liu, Jiangang</au><au>Donaldson, Joshua</au><au>Selenica, Pier</au><au>Brown, David N</au><au>Weigelt, Britta</au><au>Reis-Filho, Jorge S</au><au>Park, Ben H</au><au>Hurvitz, Sara A</au><au>Slamon, Dennis J</au><au>Rimawi, Mothaffar F</au><au>Jansen, Valerie M</au><au>Jeselsohn, Rinath</au><au>Osborne, C Kent</au><au>Schiff, Rachel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation of the IFN Signaling Pathway is Associated with Resistance to CDK4/6 Inhibitors and Immune Checkpoint Activation in ER-Positive Breast Cancer</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2021-09-01</date><risdate>2021</risdate><volume>27</volume><issue>17</issue><spage>4870</spage><epage>4882</epage><pages>4870-4882</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (CDK4/6i) are highly effective against estrogen receptor-positive (ER
)/HER2
breast cancer; however, intrinsic and acquired resistance is common. Elucidating the molecular features of sensitivity and resistance to CDK4/6i may lead to identification of predictive biomarkers and novel therapeutic targets, paving the way toward improving patient outcomes.
Parental breast cancer cells and their endocrine-resistant derivatives (EndoR) were used. Derivatives with acquired resistance to palbociclib (PalboR) were generated from parental and estrogen deprivation-resistant MCF7 and T47D cells. Transcriptomic and proteomic analyses were performed in palbociclib-sensitive and PalboR lines. Gene expression data from CDK4/6i neoadjuvant trials and publicly available datasets were interrogated for correlations of gene signatures and patient outcomes.
Parental and EndoR breast cancer lines showed varying degrees of sensitivity to palbociclib. Transcriptomic analysis of these cell lines identified an association between high IFN signaling and reduced CDK4/6i sensitivity; thus an "IFN-related palbociclib-resistance Signature" (IRPS) was derived. In two neoadjuvant trials of CDK4/6i plus endocrine therapy, IRPS and other IFN-related signatures were highly enriched in patients with tumors exhibiting intrinsic resistance to CDK4/6i. PalboR derivatives displayed dramatic activation of IFN/STAT1 signaling compared with their short-term treated or untreated counterparts. In primary ER
/HER2
tumors, the IRPS score was significantly higher in lumB than lumA subtype and correlated with increased gene expression of immune checkpoints, endocrine resistance, and poor prognosis.
Aberrant IFN signaling is associated with intrinsic resistance to CDK4/6i. Experimentally, acquired resistance to palbociclib is associated with activation of the IFN pathway, warranting additional studies to clarify its involvement in resistance to CDK4/6i.</abstract><cop>United States</cop><pmid>33536276</pmid><doi>10.1158/1078-0432.CCR-19-4191</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-7962-673X</orcidid><orcidid>https://orcid.org/0000-0003-1957-7160</orcidid><orcidid>https://orcid.org/0000-0003-1227-356X</orcidid><orcidid>https://orcid.org/0000-0003-0005-6496</orcidid><orcidid>https://orcid.org/0000-0002-4297-2997</orcidid><orcidid>https://orcid.org/0000-0002-2800-077X</orcidid><orcidid>https://orcid.org/0000-0003-1696-5213</orcidid><orcidid>https://orcid.org/0000-0001-7996-7529</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-0432 |
| ispartof | Clinical cancer research, 2021-09, Vol.27 (17), p.4870-4882 |
| issn | 1078-0432 1557-3265 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2486462198 |
| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Antineoplastic Agents - therapeutic use Breast Neoplasms - chemistry Breast Neoplasms - drug therapy Cyclin-Dependent Kinase 4 - antagonists & inhibitors Cyclin-Dependent Kinase 6 - antagonists & inhibitors Female Humans Piperazines - therapeutic use Pyridines - therapeutic use Receptors, Estrogen - analysis Signal Transduction Tumor Cells, Cultured |
| title | Activation of the IFN Signaling Pathway is Associated with Resistance to CDK4/6 Inhibitors and Immune Checkpoint Activation in ER-Positive Breast Cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T19%3A57%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Activation%20of%20the%20IFN%20Signaling%20Pathway%20is%20Associated%20with%20Resistance%20to%20CDK4/6%20Inhibitors%20and%20Immune%20Checkpoint%20Activation%20in%20ER-Positive%20Breast%20Cancer&rft.jtitle=Clinical%20cancer%20research&rft.au=De%20Angelis,%20Carmine&rft.date=2021-09-01&rft.volume=27&rft.issue=17&rft.spage=4870&rft.epage=4882&rft.pages=4870-4882&rft.issn=1078-0432&rft.eissn=1557-3265&rft_id=info:doi/10.1158/1078-0432.CCR-19-4191&rft_dat=%3Cproquest_cross%3E2486462198%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2486462198&rft_id=info:pmid/33536276&rfr_iscdi=true |