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Dual targeting of MCL1 and NOXA as effective strategy for treatment of mantle cell lymphoma
Summary Imbalances in the composition of BCL2 family proteins contribute to tumourigenesis and therapy resistance of mantle cell lymphoma (MCL), making these proteins attractive therapy targets. We studied the efficiency of dual targeting the NOXA/MCL1 axis by combining fatty acid synthase inhibitor...
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| Published in: | British journal of haematology 2017-05, Vol.177 (4), p.557-561 |
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| Main Authors: | , , , , , , , , , , , , |
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| Language: | English |
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| cites | cdi_FETCH-LOGICAL-c4541-8672872aed38328f07745aa2784181da10b6f76ab85a04b682d6333b60fcbd0a3 |
| container_end_page | 561 |
| container_issue | 4 |
| container_start_page | 557 |
| container_title | British journal of haematology |
| container_volume | 177 |
| creator | Höring, Elisabeth Montraveta, Arnau Heine, Simon Kleih, Markus Schaaf, Lea Vöhringer, Matthias C. Esteve‐Arenys, Anna Roué, Gael Colomer, Dolors Campo, Elias Ott, German Aulitzky, Walter E. Kuip, Heiko |
| description | Summary
Imbalances in the composition of BCL2 family proteins contribute to tumourigenesis and therapy resistance of mantle cell lymphoma (MCL), making these proteins attractive therapy targets. We studied the efficiency of dual targeting the NOXA/MCL1 axis by combining fatty acid synthase inhibitors (NOXA stabilization) with the CDK inhibitor Dinaciclib (MCL1 reduction). This combination synergistically induced apoptosis in cell lines and primary MCL cells and led to almost complete inhibition of tumour progression in a mouse model. Apoptosis was NOXA‐dependent and correlated with the NOXA/MCL1 ratio, highlighting the importance of the NOXA/MCL1 balance for effective cell death induction in MCL. |
| doi_str_mv | 10.1111/bjh.14571 |
| format | article |
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Imbalances in the composition of BCL2 family proteins contribute to tumourigenesis and therapy resistance of mantle cell lymphoma (MCL), making these proteins attractive therapy targets. We studied the efficiency of dual targeting the NOXA/MCL1 axis by combining fatty acid synthase inhibitors (NOXA stabilization) with the CDK inhibitor Dinaciclib (MCL1 reduction). This combination synergistically induced apoptosis in cell lines and primary MCL cells and led to almost complete inhibition of tumour progression in a mouse model. Apoptosis was NOXA‐dependent and correlated with the NOXA/MCL1 ratio, highlighting the importance of the NOXA/MCL1 balance for effective cell death induction in MCL.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1111/bjh.14571</identifier><identifier>PMID: 28295185</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Animals ; Apoptosis ; Apoptosis - drug effects ; Bridged Bicyclo Compounds, Heterocyclic - pharmacology ; Cell death ; Cell Line, Tumor ; Cyclin-Dependent Kinases - antagonists & inhibitors ; Dinaciclib ; Enzyme Inhibitors - therapeutic use ; FASNi ; Fatty-acid synthase ; Female ; Hematology ; Humans ; Lactones - pharmacology ; Lymphoma ; Lymphoma, Mantle-Cell - drug therapy ; Mantle cell lymphoma ; Mcl-1 protein ; MCL1 ; Mice, SCID ; Myeloid Cell Leukemia Sequence 1 Protein - antagonists & inhibitors ; NOXA ; Proteins ; Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors ; Pyridinium Compounds - pharmacology ; Tumorigenesis ; Tumors</subject><ispartof>British journal of haematology, 2017-05, Vol.177 (4), p.557-561</ispartof><rights>2017 John Wiley & Sons Ltd</rights><rights>2017 John Wiley & Sons Ltd.</rights><rights>Copyright © 2017 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4541-8672872aed38328f07745aa2784181da10b6f76ab85a04b682d6333b60fcbd0a3</citedby><cites>FETCH-LOGICAL-c4541-8672872aed38328f07745aa2784181da10b6f76ab85a04b682d6333b60fcbd0a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28295185$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Höring, Elisabeth</creatorcontrib><creatorcontrib>Montraveta, Arnau</creatorcontrib><creatorcontrib>Heine, Simon</creatorcontrib><creatorcontrib>Kleih, Markus</creatorcontrib><creatorcontrib>Schaaf, Lea</creatorcontrib><creatorcontrib>Vöhringer, Matthias C.</creatorcontrib><creatorcontrib>Esteve‐Arenys, Anna</creatorcontrib><creatorcontrib>Roué, Gael</creatorcontrib><creatorcontrib>Colomer, Dolors</creatorcontrib><creatorcontrib>Campo, Elias</creatorcontrib><creatorcontrib>Ott, German</creatorcontrib><creatorcontrib>Aulitzky, Walter E.</creatorcontrib><creatorcontrib>Kuip, Heiko</creatorcontrib><title>Dual targeting of MCL1 and NOXA as effective strategy for treatment of mantle cell lymphoma</title><title>British journal of haematology</title><addtitle>Br J Haematol</addtitle><description>Summary
Imbalances in the composition of BCL2 family proteins contribute to tumourigenesis and therapy resistance of mantle cell lymphoma (MCL), making these proteins attractive therapy targets. We studied the efficiency of dual targeting the NOXA/MCL1 axis by combining fatty acid synthase inhibitors (NOXA stabilization) with the CDK inhibitor Dinaciclib (MCL1 reduction). This combination synergistically induced apoptosis in cell lines and primary MCL cells and led to almost complete inhibition of tumour progression in a mouse model. Apoptosis was NOXA‐dependent and correlated with the NOXA/MCL1 ratio, highlighting the importance of the NOXA/MCL1 balance for effective cell death induction in MCL.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Bridged Bicyclo Compounds, Heterocyclic - pharmacology</subject><subject>Cell death</subject><subject>Cell Line, Tumor</subject><subject>Cyclin-Dependent Kinases - antagonists & inhibitors</subject><subject>Dinaciclib</subject><subject>Enzyme Inhibitors - therapeutic use</subject><subject>FASNi</subject><subject>Fatty-acid synthase</subject><subject>Female</subject><subject>Hematology</subject><subject>Humans</subject><subject>Lactones - pharmacology</subject><subject>Lymphoma</subject><subject>Lymphoma, Mantle-Cell - drug therapy</subject><subject>Mantle cell lymphoma</subject><subject>Mcl-1 protein</subject><subject>MCL1</subject><subject>Mice, SCID</subject><subject>Myeloid Cell Leukemia Sequence 1 Protein - antagonists & inhibitors</subject><subject>NOXA</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors</subject><subject>Pyridinium Compounds - pharmacology</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNp1kE1PGzEQQK0KBIFy4A8gS1zKYcHjtdfOMU35KEqbSytV6sGa3bWTjfYjtb2g_Hs2JOWAxFzm8uZp9Ag5B3YNw9zkq-U1CKngExlBmsmEg4ADMmKMqQSY0MfkJIQVY5AyCUfkmGs-lqDliPz91mNNI_qFjVW7oJ2jP6YzoNiW9Of8z4RioNY5W8TqydIQPUa72FDXeRq9xdjYNm6PGmxjbWlh65rWm2a97Br8TA4d1sGe7fcp-X13-2v6kMzm99-nk1lSCCkg0ZniWnG0ZapTrh1TSkhErrQADSUCyzOnMsy1RCbyTPMyS9M0z5gr8pJhekq-7Lxr3_3rbYimqcL2E2xt1wcDWiktpVRsQC_foauu9-3wnYExZ0KobAwDdbWjCt-F4K0za1816DcGmNkWN0Nx81p8YC_2xj5vbPlG_k88ADc74Lmq7eZjk_n6-LBTvgCayYeV</recordid><startdate>201705</startdate><enddate>201705</enddate><creator>Höring, Elisabeth</creator><creator>Montraveta, Arnau</creator><creator>Heine, Simon</creator><creator>Kleih, Markus</creator><creator>Schaaf, Lea</creator><creator>Vöhringer, Matthias C.</creator><creator>Esteve‐Arenys, Anna</creator><creator>Roué, Gael</creator><creator>Colomer, Dolors</creator><creator>Campo, Elias</creator><creator>Ott, German</creator><creator>Aulitzky, Walter E.</creator><creator>Kuip, Heiko</creator><general>Blackwell Publishing Ltd</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>201705</creationdate><title>Dual targeting of MCL1 and NOXA as effective strategy for treatment of mantle cell lymphoma</title><author>Höring, Elisabeth ; Montraveta, Arnau ; Heine, Simon ; Kleih, Markus ; Schaaf, Lea ; Vöhringer, Matthias C. ; Esteve‐Arenys, Anna ; Roué, Gael ; Colomer, Dolors ; Campo, Elias ; Ott, German ; Aulitzky, Walter E. ; Kuip, Heiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4541-8672872aed38328f07745aa2784181da10b6f76ab85a04b682d6333b60fcbd0a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Bridged Bicyclo Compounds, Heterocyclic - pharmacology</topic><topic>Cell death</topic><topic>Cell Line, Tumor</topic><topic>Cyclin-Dependent Kinases - antagonists & inhibitors</topic><topic>Dinaciclib</topic><topic>Enzyme Inhibitors - therapeutic use</topic><topic>FASNi</topic><topic>Fatty-acid synthase</topic><topic>Female</topic><topic>Hematology</topic><topic>Humans</topic><topic>Lactones - pharmacology</topic><topic>Lymphoma</topic><topic>Lymphoma, Mantle-Cell - drug therapy</topic><topic>Mantle cell lymphoma</topic><topic>Mcl-1 protein</topic><topic>MCL1</topic><topic>Mice, SCID</topic><topic>Myeloid Cell Leukemia Sequence 1 Protein - antagonists & inhibitors</topic><topic>NOXA</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors</topic><topic>Pyridinium Compounds - pharmacology</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Höring, Elisabeth</creatorcontrib><creatorcontrib>Montraveta, Arnau</creatorcontrib><creatorcontrib>Heine, Simon</creatorcontrib><creatorcontrib>Kleih, Markus</creatorcontrib><creatorcontrib>Schaaf, Lea</creatorcontrib><creatorcontrib>Vöhringer, Matthias C.</creatorcontrib><creatorcontrib>Esteve‐Arenys, Anna</creatorcontrib><creatorcontrib>Roué, Gael</creatorcontrib><creatorcontrib>Colomer, Dolors</creatorcontrib><creatorcontrib>Campo, Elias</creatorcontrib><creatorcontrib>Ott, German</creatorcontrib><creatorcontrib>Aulitzky, Walter E.</creatorcontrib><creatorcontrib>Kuip, Heiko</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Höring, Elisabeth</au><au>Montraveta, Arnau</au><au>Heine, Simon</au><au>Kleih, Markus</au><au>Schaaf, Lea</au><au>Vöhringer, Matthias C.</au><au>Esteve‐Arenys, Anna</au><au>Roué, Gael</au><au>Colomer, Dolors</au><au>Campo, Elias</au><au>Ott, German</au><au>Aulitzky, Walter E.</au><au>Kuip, Heiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dual targeting of MCL1 and NOXA as effective strategy for treatment of mantle cell lymphoma</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2017-05</date><risdate>2017</risdate><volume>177</volume><issue>4</issue><spage>557</spage><epage>561</epage><pages>557-561</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><abstract>Summary
Imbalances in the composition of BCL2 family proteins contribute to tumourigenesis and therapy resistance of mantle cell lymphoma (MCL), making these proteins attractive therapy targets. We studied the efficiency of dual targeting the NOXA/MCL1 axis by combining fatty acid synthase inhibitors (NOXA stabilization) with the CDK inhibitor Dinaciclib (MCL1 reduction). This combination synergistically induced apoptosis in cell lines and primary MCL cells and led to almost complete inhibition of tumour progression in a mouse model. Apoptosis was NOXA‐dependent and correlated with the NOXA/MCL1 ratio, highlighting the importance of the NOXA/MCL1 balance for effective cell death induction in MCL.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>28295185</pmid><doi>10.1111/bjh.14571</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | Wiley |
| subjects | Animals Apoptosis Apoptosis - drug effects Bridged Bicyclo Compounds, Heterocyclic - pharmacology Cell death Cell Line, Tumor Cyclin-Dependent Kinases - antagonists & inhibitors Dinaciclib Enzyme Inhibitors - therapeutic use FASNi Fatty-acid synthase Female Hematology Humans Lactones - pharmacology Lymphoma Lymphoma, Mantle-Cell - drug therapy Mantle cell lymphoma Mcl-1 protein MCL1 Mice, SCID Myeloid Cell Leukemia Sequence 1 Protein - antagonists & inhibitors NOXA Proteins Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors Pyridinium Compounds - pharmacology Tumorigenesis Tumors |
| title | Dual targeting of MCL1 and NOXA as effective strategy for treatment of mantle cell lymphoma |
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