Pan-HER, an Antibody Mixture Simultaneously Targeting EGFR, HER2, and HER3, Effectively Overcomes Tumor Heterogeneity and Plasticity
Accumulating evidence indicates a high degree of plasticity and compensatory signaling within the human epidermal growth factor receptor (HER) family, leading to resistance upon therapeutic intervention with HER family members. We have generated Pan-HER, a mixture of six antibodies targeting each of...
Saved in:
Published in | Clinical cancer research Vol. 21; no. 18; pp. 4110 - 4122 |
---|---|
Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
15.09.2015
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Accumulating evidence indicates a high degree of plasticity and compensatory signaling within the human epidermal growth factor receptor (HER) family, leading to resistance upon therapeutic intervention with HER family members.
We have generated Pan-HER, a mixture of six antibodies targeting each of the HER family members EGFR, HER2, and HER3 with synergistic pairs of antibodies, which simultaneously remove all three targets, thereby preventing compensatory tumor promoting mechanisms within the HER family. Pan-HER induces potent growth inhibition in a range of cancer cell lines and xenograft models, including cell lines with acquired resistance to therapeutic antibodies. Pan-HER is also highly efficacious in the presence of HER family ligands, indicating that it is capable of overcoming acquired resistance due to increased ligand production. All three target specificities contribute to the enhanced efficacy, demonstrating a distinct benefit of combined HER family targeting when compared with single-receptor targeting.
Our data show that simultaneous targeting of three receptors provides broader efficacy than targeting a single receptor or any combination of two receptors in the HER family, especially in the presence of HER family ligands. Pan-HER represents a novel strategy to deal with primary and acquired resistance due to tumor heterogeneity and plasticity in terms of HER family dependency and as such may be a viable alternative in the clinic. |
---|---|
AbstractList | PURPOSEAccumulating evidence indicates a high degree of plasticity and compensatory signaling within the human epidermal growth factor receptor (HER) family, leading to resistance upon therapeutic intervention with HER family members. EXPERIMENTAL DESIGN/RESULTSWe have generated Pan-HER, a mixture of six antibodies targeting each of the HER family members EGFR, HER2, and HER3 with synergistic pairs of antibodies, which simultaneously remove all three targets, thereby preventing compensatory tumor promoting mechanisms within the HER family. Pan-HER induces potent growth inhibition in a range of cancer cell lines and xenograft models, including cell lines with acquired resistance to therapeutic antibodies. Pan-HER is also highly efficacious in the presence of HER family ligands, indicating that it is capable of overcoming acquired resistance due to increased ligand production. All three target specificities contribute to the enhanced efficacy, demonstrating a distinct benefit of combined HER family targeting when compared with single-receptor targeting. CONCLUSIONSOur data show that simultaneous targeting of three receptors provides broader efficacy than targeting a single receptor or any combination of two receptors in the HER family, especially in the presence of HER family ligands. Pan-HER represents a novel strategy to deal with primary and acquired resistance due to tumor heterogeneity and plasticity in terms of HER family dependency and as such may be a viable alternative in the clinic. Accumulating evidence indicates a high degree of plasticity and compensatory signaling within the human epidermal growth factor receptor (HER) family, leading to resistance upon therapeutic intervention with HER family members. We have generated Pan-HER, a mixture of six antibodies targeting each of the HER family members EGFR, HER2, and HER3 with synergistic pairs of antibodies, which simultaneously remove all three targets, thereby preventing compensatory tumor promoting mechanisms within the HER family. Pan-HER induces potent growth inhibition in a range of cancer cell lines and xenograft models, including cell lines with acquired resistance to therapeutic antibodies. Pan-HER is also highly efficacious in the presence of HER family ligands, indicating that it is capable of overcoming acquired resistance due to increased ligand production. All three target specificities contribute to the enhanced efficacy, demonstrating a distinct benefit of combined HER family targeting when compared with single-receptor targeting. Our data show that simultaneous targeting of three receptors provides broader efficacy than targeting a single receptor or any combination of two receptors in the HER family, especially in the presence of HER family ligands. Pan-HER represents a novel strategy to deal with primary and acquired resistance due to tumor heterogeneity and plasticity in terms of HER family dependency and as such may be a viable alternative in the clinic. Purpose: Accumulating evidence indicates a high degree of plasticity and compensatory signaling within the human epidermal growth factor receptor (HER) family, leading to resistance upon therapeutic intervention with HER family members. Experimental Design/Results: We have generated Pan-HER, a mixture of six antibodies targeting each of the HER family members EGFR, HER2, and HER3 with synergistic pairs of antibodies, which simultaneously remove all three targets, thereby preventing compensatory tumor promoting mechanisms within the HER family. Pan-HER induces potent growth inhibition in a range of cancer cell lines and xenograft models, including cell lines with acquired resistance to therapeutic antibodies. Pan-HER is also highly efficacious in the presence of HER family ligands, indicating that it is capable of overcoming acquired resistance due to increased ligand production. All three target specificities contribute to the enhanced efficacy, demonstrating a distinct benefit of combined HER family targeting when compared with single-receptor targeting. Conclusions: Our data show that simultaneous targeting of three receptors provides broader efficacy than targeting a single receptor or any combination of two receptors in the HER family, especially in the presence of HER family ligands. Pan-HER represents a novel strategy to deal with primary and acquired resistance due to tumor heterogeneity and plasticity in terms of HER family dependency and as such may be a viable alternative in the clinic. Clin Cancer Res; 21(18); 4110–22. ©2015 AACR. See related commentary by Yarden and Sela, p. 4030 Purpose: Accumulating evidence indicates a high degree of plasticity and compensatory signaling within the human epidermal growth factor receptor (HER) family, leading to resistance upon therapeutic intervention with HER family members.Experimental Design/Results: We have generated Pan-HER, a mixture of six antibodies targeting each of the HER family members EGFR, HER2, and HER3 with synergistic pairs of antibodies, which simultaneously remove all three targets, thereby preventing compensatory tumor promoting mechanisms within the HER family. Pan-HER induces potent growth inhibition in a range of cancer cell lines and xenograft models, including cell lines with acquired resistance to therapeutic antibodies. Pan-HER is also highly efficacious in the presence of HER family ligands, indicating that it is capable of overcoming acquired resistance due to increased ligand production. All three target specificities contribute to the enhanced efficacy, demonstrating a distinct benefit of combined HER family targeting when compared with single-receptor targeting.Conclusions: Our data show that simultaneous targeting of three receptors provides broader efficacy than targeting a single receptor or any combination of two receptors in the HER family, especially in the presence of HER family ligands. Pan-HER represents a novel strategy to deal with primary and acquired resistance due to tumor heterogeneity and plasticity in terms of HER family dependency and as such may be a viable alternative in the clinic. Clin Cancer Res; 21(18); 4110-22. copyright 2015 AACR.See related commentary by Yarden and Sela, p. 4030 |
Author | Kjær, Ida Poulsen, Thomas T Jacobsen, Helle J Koefoed, Klaus Kragh, Michael Pedersen, Mikkel W Weilguny, Dietmar Dahlman, Anna Sen, Jette W Horak, Ivan D Andersen, Christina R Lantto, Johan Bjerregaard, Bolette |
Author_xml | – sequence: 1 givenname: Helle J surname: Jacobsen fullname: Jacobsen, Helle J organization: Symphogen A/S, Ballerup, Denmark – sequence: 2 givenname: Thomas T surname: Poulsen fullname: Poulsen, Thomas T organization: Symphogen A/S, Ballerup, Denmark – sequence: 3 givenname: Anna surname: Dahlman fullname: Dahlman, Anna organization: Symphogen A/S, Ballerup, Denmark – sequence: 4 givenname: Ida surname: Kjær fullname: Kjær, Ida organization: Symphogen A/S, Ballerup, Denmark – sequence: 5 givenname: Klaus surname: Koefoed fullname: Koefoed, Klaus organization: Symphogen A/S, Ballerup, Denmark – sequence: 6 givenname: Jette W surname: Sen fullname: Sen, Jette W organization: Symphogen A/S, Ballerup, Denmark – sequence: 7 givenname: Dietmar surname: Weilguny fullname: Weilguny, Dietmar organization: Symphogen A/S, Ballerup, Denmark – sequence: 8 givenname: Bolette surname: Bjerregaard fullname: Bjerregaard, Bolette organization: Symphogen A/S, Ballerup, Denmark – sequence: 9 givenname: Christina R surname: Andersen fullname: Andersen, Christina R organization: Symphogen A/S, Ballerup, Denmark – sequence: 10 givenname: Ivan D surname: Horak fullname: Horak, Ivan D organization: Symphogen A/S, Ballerup, Denmark – sequence: 11 givenname: Mikkel W surname: Pedersen fullname: Pedersen, Mikkel W organization: Symphogen A/S, Ballerup, Denmark – sequence: 12 givenname: Michael surname: Kragh fullname: Kragh, Michael organization: Symphogen A/S, Ballerup, Denmark – sequence: 13 givenname: Johan surname: Lantto fullname: Lantto, Johan email: jol@symphogen.com organization: Symphogen A/S, Ballerup, Denmark. jol@symphogen.com |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25908781$$D View this record in MEDLINE/PubMed |
BookMark | eNqFkU1P3DAQhi1ExVf7E1r52AOhntiO7SNaLSwSFYhuz5Y3maxc5YPaDmLv_HAcFnrtxTMjvY9Ho-eUHA7jgIR8BXYBIPUPYEoXTPDyYrF4KEAUnEN5QE5ASlXwspKHuf_IHJPTGP8wBgKYOCLHpTRMKw0n5OXeDcVq-XBO3UAvh-Q3Y7OjP_1zmgLSX76fuuQGHKfY7ejahS0mP2zp8voqI5krZ7CZO35Ol22LdfJPmLN3TxjqscdI11M_BrrChGHc4oA-7d6Y-87F5Os8fiafWtdF_PJez8jvq-V6sSpu765vFpe3Rc21SUWj6sZwDcpJhhvTctaCqERVGqkYcDTGOcbNRlRS1tAYcMhlPlhV-TWq4mfk-_7fxzD-nTAm2_tYY9ftL7Sgma4UE5X5f1QBl6UWUuao3EfrMMYYsLWPwfcu7CwwO7uyswc7e7DZlQVhZ1eZ-_a-Ytr02PyjPuTwV2CSjvE |
CitedBy_id | crossref_primary_10_1080_19420862_2021_1914883 crossref_primary_10_1038_s41573_022_00501_8 crossref_primary_10_1080_21645515_2015_1102809 crossref_primary_10_1038_s41598_020_59818_2 crossref_primary_10_1111_jphp_12911 crossref_primary_10_1007_s10637_022_01217_7 crossref_primary_10_1186_s13058_015_0662_4 crossref_primary_10_18632_oncotarget_20472 crossref_primary_10_1002_cbin_11340 crossref_primary_10_1158_1078_0432_CCR_17_0782 crossref_primary_10_1186_s13046_022_02515_x crossref_primary_10_3390_ijms21239008 crossref_primary_10_3390_cancers13184620 crossref_primary_10_1051_medsci_2019216 crossref_primary_10_1158_1078_0432_CCR_15_1664 crossref_primary_10_18632_oncotarget_21718 crossref_primary_10_1080_17425247_2018_1424825 crossref_primary_10_1111_jcmm_12899 crossref_primary_10_1158_1078_0432_CCR_20_4465 crossref_primary_10_1097_MD_0000000000012317 crossref_primary_10_1016_j_celrep_2020_108657 crossref_primary_10_1016_j_jtho_2019_09_195 crossref_primary_10_1126_scitranslmed_aao2301 crossref_primary_10_18632_oncotarget_6060 crossref_primary_10_1016_j_bbrc_2019_03_204 crossref_primary_10_3389_fimmu_2023_1168444 crossref_primary_10_1016_j_omtn_2017_12_015 crossref_primary_10_1021_acs_molpharmaceut_8b00388 crossref_primary_10_1016_j_coi_2016_03_001 crossref_primary_10_1158_1535_7163_MCT_18_0341 crossref_primary_10_1186_s13058_020_01280_z crossref_primary_10_1158_2159_8290_CD_17_0343 crossref_primary_10_1126_scitranslmed_aax8313 crossref_primary_10_1080_14737140_2020_1829485 crossref_primary_10_1158_1078_0432_CCR_15_0996 crossref_primary_10_1158_1535_7163_MCT_17_0374 crossref_primary_10_1111_imcb_12324 crossref_primary_10_1016_j_canlet_2018_07_014 crossref_primary_10_1007_s11060_018_2832_6 crossref_primary_10_1016_j_semcdb_2016_01_001 crossref_primary_10_1016_j_semcdb_2016_09_003 crossref_primary_10_1159_000479981 crossref_primary_10_18632_oncotarget_22825 crossref_primary_10_4081_oncol_2018_355 crossref_primary_10_1021_acs_molpharmaceut_2c00534 crossref_primary_10_1093_protein_gzw037 crossref_primary_10_1186_s13045_020_00958_3 crossref_primary_10_1158_1535_7163_MCT_21_0818 crossref_primary_10_18632_oncotarget_27671 crossref_primary_10_1124_pharmrev_123_000906 crossref_primary_10_3390_cancers14010154 crossref_primary_10_1016_j_ccell_2021_06_001 crossref_primary_10_1038_s41598_018_27454_6 crossref_primary_10_3390_toxins10080309 crossref_primary_10_1111_bph_13450 crossref_primary_10_3390_vaccines7030103 crossref_primary_10_1158_1535_7163_MCT_15_0565 crossref_primary_10_1158_1535_7163_MCT_19_0455 crossref_primary_10_1016_j_semcdb_2015_09_018 crossref_primary_10_1158_1535_7163_MCT_16_0012 crossref_primary_10_1007_s13402_019_00448_w crossref_primary_10_1038_s41467_021_23948_6 crossref_primary_10_1093_noajnl_vdz024 crossref_primary_10_3390_biology12070957 crossref_primary_10_1093_jnci_djx065 crossref_primary_10_1002_ijc_30242 |
Cites_doi | 10.1158/1078-0432.CCR-06-2302 10.1016/j.pharmthera.2014.01.005 10.1038/nrc1609 10.4161/mabs.3.4.16615 10.1126/scitranslmed.3002442 10.1158/1535-7163.MCT-13-1093 10.1016/j.ccr.2011.11.005 10.1158/1078-0432.CCR-12-2024 10.1371/journal.pone.0040285 10.4161/mabs.3.6.17955 10.1007/s12013-011-9286-1 10.1158/1078-0432.CCR-07-0701 10.4161/cbt.11.9.15050 10.1158/0008-5472.CAN-13-0099 10.1093/emboj/16.7.1647 10.1158/1535-7163.MCT-14-0697 10.1128/MCB.16.10.5276 10.1073/pnas.0409610102 10.1126/scisignal.2000352 10.1007/978-1-59745-554-1_13 10.1073/pnas.1016140108 10.1038/nature05474 10.1016/j.ccr.2011.09.003 10.1158/0008-5472.CAN-09-1417 10.1309/AJCPXTZSKBRIP07W 10.1517/14728222.2011.648617 10.1159/000319020 10.1038/nrc3559 10.1158/1535-7163.MCT-11-0820 10.1038/nature01392 10.1016/j.ceb.2007.02.008 10.1158/2159-8290.CD-12-0349 10.1016/j.ccr.2013.04.012 10.1158/0008-5472.CAN-08-1056 10.1038/nrc2656 10.1002/j.1460-2075.1996.tb00603.x 10.1038/nm.2609 10.1016/S1097-2765(03)00048-0 10.1016/j.ccr.2011.10.006 10.1038/nrc3261 10.1016/j.bcp.2012.07.011 10.2165/11537830-000000000-00000 10.1146/annurev-pathol-020712-163923 10.1007/s00262-005-0058-x 10.1073/pnas.1313857110 10.1073/pnas.1114033109 10.1016/S1535-6108(04)00083-2 10.1016/j.jmb.2006.02.040 10.1593/neo.111602 |
ContentType | Journal Article |
Copyright | 2015 American Association for Cancer Research. |
Copyright_xml | – notice: 2015 American Association for Cancer Research. |
DBID | CGR CUY CVF ECM EIF NPM AAYXX CITATION 7X8 7QO 8FD FR3 P64 |
DOI | 10.1158/1078-0432.CCR-14-3312 |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed CrossRef MEDLINE - Academic Biotechnology Research Abstracts Technology Research Database Engineering Research Database Biotechnology and BioEngineering Abstracts |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) CrossRef MEDLINE - Academic Engineering Research Database Biotechnology Research Abstracts Technology Research Database Biotechnology and BioEngineering Abstracts |
DatabaseTitleList | MEDLINE - Academic MEDLINE CrossRef Engineering Research Database |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Medicine |
EISSN | 1557-3265 |
EndPage | 4122 |
ExternalDocumentID | 10_1158_1078_0432_CCR_14_3312 25908781 |
Genre | Journal Article |
GroupedDBID | --- 18M 29B 2FS 2WC 34G 39C 476 53G 5GY 5RE 5VS 6J9 ABOCM ACGFO ACIWK ACPRK ACSVP ADBBV ADCOW ADNWM AENEX AFHIN AFOSN AFRAH ALMA_UNASSIGNED_HOLDINGS BAWUL BR6 BTFSW CGR CS3 CUY CVF DIK DU5 E3Z EBS ECM EIF EJD F5P FRP GX1 H13 IH2 KQ8 L7B LSO NPM OK1 P0W P2P QTD RCR RHF RHI RNS SJN TR2 W2D W8F WOQ YKV AAYXX CITATION 7X8 7QO 8FD FR3 P64 |
ID | FETCH-LOGICAL-c389t-d7cd93817a50eb9f30f146462957013e99aa039b4655c1d91ae35104765109763 |
ISSN | 1078-0432 |
IngestDate | Fri Oct 25 01:17:13 EDT 2024 Fri Aug 16 23:33:11 EDT 2024 Thu Nov 21 22:45:17 EST 2024 Sat Sep 28 08:22:14 EDT 2024 |
IsDoiOpenAccess | false |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 18 |
Language | English |
License | 2015 American Association for Cancer Research. |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-c389t-d7cd93817a50eb9f30f146462957013e99aa039b4655c1d91ae35104765109763 |
Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
OpenAccessLink | https://doi.org/10.1158/1078-0432.22457516 |
PMID | 25908781 |
PQID | 1713528455 |
PQPubID | 23479 |
PageCount | 13 |
ParticipantIDs | proquest_miscellaneous_1808670469 proquest_miscellaneous_1713528455 crossref_primary_10_1158_1078_0432_CCR_14_3312 pubmed_primary_25908781 |
PublicationCentury | 2000 |
PublicationDate | 2015-Sep-15 2015-09-15 20150915 |
PublicationDateYYYYMMDD | 2015-09-15 |
PublicationDate_xml | – month: 09 year: 2015 text: 2015-Sep-15 day: 15 |
PublicationDecade | 2010 |
PublicationPlace | United States |
PublicationPlace_xml | – name: United States |
PublicationTitle | Clinical cancer research |
PublicationTitleAlternate | Clin Cancer Res |
PublicationYear | 2015 |
References | 26019173 - Clin Cancer Res. 2015 Sep 15;21(18):4030-2 Tzahar (2022061102283936300_bib47) 1996; 16 Schaefer (2022061102283936300_bib37) 2011; 20 Meijer (2022061102283936300_bib30) 2006; 358 Seshacharyulu (2022061102283936300_bib4) 2012; 16 Pinkas-Kramarski (2022061102283936300_bib46) 1996; 15 Schoeberl (2022061102283936300_bib32) 2009; 2 Tebbutt (2022061102283936300_bib5) 2013; 13 Larbouret (2022061102283936300_bib36) 2012; 14 Jaiswal (2022061102283936300_bib42) 2013; 23 Szerlip (2022061102283936300_bib21) 2012; 109 Pedersen (2022061102283936300_bib28) 2015; 14 Bose (2022061102283936300_bib41) 2013; 3 Marusyk (2022061102283936300_bib18) 2012; 12 Sergina (2022061102283936300_bib12) 2007; 445 Narayan (2022061102283936300_bib14) 2009; 69 Almendro (2022061102283936300_bib19) 2013; 8 Maron (2022061102283936300_bib38) 2013; 110 Yonesaka (2022061102283936300_bib16) 2011; 3 Kol (2022061102283936300_bib6) 2014; 143 Koefoed (2022061102283936300_bib29) 2011; 3 McDonagh (2022061102283936300_bib39) 2012; 11 Graus-Porta (2022061102283936300_bib45) 1997; 16 Malinowsky (2022061102283936300_bib25) 2012; 7 Cho (2022061102283936300_bib44) 2003; 421 Demarest (2022061102283936300_bib8) 2011; 3 Garrett (2022061102283936300_bib15) 2011; 108 Adams (2022061102283936300_bib33) 2006; 55 Larbouret (2022061102283936300_bib35) 2007; 13 Brand (2022061102283936300_bib11) 2011; 11 Montagut (2022061102283936300_bib40) 2012; 18 Garrett (2022061102283936300_bib43) 2003; 11 May (2022061102283936300_bib9) 2012; 84 Kaneko (2022061102283936300_bib49) 2011; 25 Franklin (2022061102283936300_bib7) 2004; 5 Davila (2022061102283936300_bib22) 2010; 3 Pedersen (2022061102283936300_bib27) 2010; 70 Baselga (2022061102283936300_bib2) 2009; 9 Kasprzyk (2022061102283936300_bib34) 1992; 52 Snuderl (2022061102283936300_bib20) 2011; 20 Hynes (2022061102283936300_bib3) 2005; 5 Yang (2022061102283936300_bib24) 2012; 62 Vlacich (2022061102283936300_bib10) 2011; 20 Garrett (2022061102283936300_bib17) 2013; 19 Allison (2022061102283936300_bib23) 2011; 136 Ritter (2022061102283936300_bib13) 2007; 13 Meijer (2022061102283936300_bib31) 2009; 525 Bublil (2022061102283936300_bib1) 2007; 19 Mirschberger (2022061102283936300_bib50) 2013; 73 Friedman (2022061102283936300_bib26) 2005; 102 Jiang (2022061102283936300_bib48) 2014; 13 |
References_xml | – volume: 13 start-page: 3356 year: 2007 ident: 2022061102283936300_bib35 article-title: In vivo therapeutic synergism of anti-epidermal growth factor receptor and anti-HER2 monoclonal antibodies against pancreatic carcinomas publication-title: Clin Cancer Res doi: 10.1158/1078-0432.CCR-06-2302 contributor: fullname: Larbouret – volume: 143 start-page: 1 year: 2014 ident: 2022061102283936300_bib6 article-title: HER3, serious partner in crime: therapeutic approaches and potential biomarkers for effect of HER3-targeting publication-title: Pharmacol Ther doi: 10.1016/j.pharmthera.2014.01.005 contributor: fullname: Kol – volume: 5 start-page: 341 year: 2005 ident: 2022061102283936300_bib3 article-title: ERBB receptors and cancer: the complexity of targeted inhibitors publication-title: Nat Rev Cancer doi: 10.1038/nrc1609 contributor: fullname: Hynes – volume: 3 start-page: 338 year: 2011 ident: 2022061102283936300_bib8 article-title: Emerging antibody combinations in oncology publication-title: MAbs doi: 10.4161/mabs.3.4.16615 contributor: fullname: Demarest – volume: 3 start-page: 99ra86 year: 2011 ident: 2022061102283936300_bib16 article-title: Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab publication-title: Sci Transl Med doi: 10.1126/scitranslmed.3002442 contributor: fullname: Yonesaka – volume: 13 start-page: 1826 year: 2014 ident: 2022061102283936300_bib48 article-title: Combination of anti-HER3 antibody MM-121/SAR256212 and cetuximab inhibits tumor growth in preclinical models of head and neck squamous cell carcinoma publication-title: Mol Cancer Ther doi: 10.1158/1535-7163.MCT-13-1093 contributor: fullname: Jiang – volume: 20 start-page: 810 year: 2011 ident: 2022061102283936300_bib20 article-title: Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma publication-title: Cancer Cell doi: 10.1016/j.ccr.2011.11.005 contributor: fullname: Snuderl – volume: 19 start-page: 610 year: 2013 ident: 2022061102283936300_bib17 article-title: Dual blockade of HER2 in HER2-overexpressing tumor cells does not completely eliminate HER3 function publication-title: Clin Cancer Res doi: 10.1158/1078-0432.CCR-12-2024 contributor: fullname: Garrett – volume: 7 start-page: e40285 year: 2012 ident: 2022061102283936300_bib25 article-title: Common protein biomarkers assessed by reverse phase protein arrays show considerable intratumoral heterogeneity in breast cancer tissues publication-title: PLoS ONE doi: 10.1371/journal.pone.0040285 contributor: fullname: Malinowsky – volume: 52 start-page: 2771 year: 1992 ident: 2022061102283936300_bib34 article-title: Therapy of an animal model of human gastric cancer using a combination of anti-erbB-2 monoclonal antibodies publication-title: Cancer Res contributor: fullname: Kasprzyk – volume: 3 start-page: 584 year: 2011 ident: 2022061102283936300_bib29 article-title: Rational identification of an optimal antibody mixture for targeting the epidermal growth factor receptor publication-title: MAbs doi: 10.4161/mabs.3.6.17955 contributor: fullname: Koefoed – volume: 62 start-page: 221 year: 2012 ident: 2022061102283936300_bib24 article-title: Intratumoral heterogeneity determines discordant results of diagnostic tests for human epidermal growth factor receptor (HER) 2 in gastric cancer specimens publication-title: Cell Biochem Biophys doi: 10.1007/s12013-011-9286-1 contributor: fullname: Yang – volume: 13 start-page: 4909 year: 2007 ident: 2022061102283936300_bib13 article-title: Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network publication-title: Clin Cancer Res doi: 10.1158/1078-0432.CCR-07-0701 contributor: fullname: Ritter – volume: 11 start-page: 777 year: 2011 ident: 2022061102283936300_bib11 article-title: Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab publication-title: Cancer Biol Ther doi: 10.4161/cbt.11.9.15050 contributor: fullname: Brand – volume: 73 start-page: 5183 year: 2013 ident: 2022061102283936300_bib50 article-title: RG7116, a therapeutic antibody that binds the inactive HER3 receptor and is optimized for immune effector activation publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-13-0099 contributor: fullname: Mirschberger – volume: 16 start-page: 1647 year: 1997 ident: 2022061102283936300_bib45 article-title: ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling publication-title: EMBO J doi: 10.1093/emboj/16.7.1647 contributor: fullname: Graus-Porta – volume: 14 start-page: 669 year: 2015 ident: 2022061102283936300_bib28 article-title: Targeting three distinct HER2 domains with a recombinant antibody mixture overcomes trastuzumab resistance publication-title: Mol Cancer Ther doi: 10.1158/1535-7163.MCT-14-0697 contributor: fullname: Pedersen – volume: 16 start-page: 5276 year: 1996 ident: 2022061102283936300_bib47 article-title: A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor publication-title: Mol Cell Biol doi: 10.1128/MCB.16.10.5276 contributor: fullname: Tzahar – volume: 102 start-page: 1915 year: 2005 ident: 2022061102283936300_bib26 article-title: Synergistic down-regulation of receptor tyrosine kinases by combinations of mAbs: implications for cancer immunotherapy publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.0409610102 contributor: fullname: Friedman – volume: 2 start-page: ra31 year: 2009 ident: 2022061102283936300_bib32 article-title: Therapeutically targeting ErbB3: a key node in ligand-induced activation of the ErbB receptor-PI3K axis publication-title: Sci Signal doi: 10.1126/scisignal.2000352 contributor: fullname: Schoeberl – volume: 525 start-page: 261 year: 2009 ident: 2022061102283936300_bib31 article-title: Human antibody repertoires publication-title: Methods Mol Biol doi: 10.1007/978-1-59745-554-1_13 contributor: fullname: Meijer – volume: 108 start-page: 5021 year: 2011 ident: 2022061102283936300_bib15 article-title: Transcriptional and posttranslational up-regulation of HER3 (ErbB3) compensates for inhibition of the HER2 tyrosine kinase publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.1016140108 contributor: fullname: Garrett – volume: 445 start-page: 437 year: 2007 ident: 2022061102283936300_bib12 article-title: Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3 publication-title: Nature doi: 10.1038/nature05474 contributor: fullname: Sergina – volume: 20 start-page: 472 year: 2011 ident: 2022061102283936300_bib37 article-title: A two-in-one antibody against HER3 and EGFR has superior inhibitory activity compared with monospecific antibodies publication-title: Cancer Cell doi: 10.1016/j.ccr.2011.09.003 contributor: fullname: Schaefer – volume: 70 start-page: 588 year: 2010 ident: 2022061102283936300_bib27 article-title: Sym004: a novel synergistic anti-epidermal growth factor receptor antibody mixture with superior anticancer efficacy publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-09-1417 contributor: fullname: Pedersen – volume: 136 start-page: 864 year: 2011 ident: 2022061102283936300_bib23 article-title: Frequency of HER2 heterogeneity by fluorescence in situ hybridization according to CAP expert panel recommendations: time for a new look at how to report heterogeneity publication-title: Am J Clin Pathol doi: 10.1309/AJCPXTZSKBRIP07W contributor: fullname: Allison – volume: 16 start-page: 15 year: 2012 ident: 2022061102283936300_bib4 article-title: Targeting the EGFR signaling pathway in cancer therapy publication-title: Expert Opin Ther Targets doi: 10.1517/14728222.2011.648617 contributor: fullname: Seshacharyulu – volume: 3 start-page: 268 year: 2010 ident: 2022061102283936300_bib22 article-title: The Clinical Importance of the Heterogeneity of HER2 neu publication-title: Case Rep Oncol doi: 10.1159/000319020 contributor: fullname: Davila – volume: 13 start-page: 663 year: 2013 ident: 2022061102283936300_bib5 article-title: Targeting the ERBB family in cancer: couples therapy publication-title: Nat Rev Cancer doi: 10.1038/nrc3559 contributor: fullname: Tebbutt – volume: 11 start-page: 582 year: 2012 ident: 2022061102283936300_bib39 article-title: Antitumor activity of a novel bispecific antibody that targets the ErbB2/ErbB3 oncogenic unit and inhibits heregulin-induced activation of ErbB3 publication-title: Mol Cancer Ther doi: 10.1158/1535-7163.MCT-11-0820 contributor: fullname: McDonagh – volume: 421 start-page: 756 year: 2003 ident: 2022061102283936300_bib44 article-title: Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab publication-title: Nature doi: 10.1038/nature01392 contributor: fullname: Cho – volume: 19 start-page: 124 year: 2007 ident: 2022061102283936300_bib1 article-title: The EGF receptor family: spearheading a merger of signaling and therapeutics publication-title: Curr Opin Cell Biol doi: 10.1016/j.ceb.2007.02.008 contributor: fullname: Bublil – volume: 3 start-page: 224 year: 2013 ident: 2022061102283936300_bib41 article-title: Activating HER2 mutations in HER2 gene amplification negative breast cancer publication-title: Cancer Discov doi: 10.1158/2159-8290.CD-12-0349 contributor: fullname: Bose – volume: 23 start-page: 603 year: 2013 ident: 2022061102283936300_bib42 article-title: Oncogenic ERBB3 mutations in human cancers publication-title: Cancer Cell doi: 10.1016/j.ccr.2013.04.012 contributor: fullname: Jaiswal – volume: 69 start-page: 2191 year: 2009 ident: 2022061102283936300_bib14 article-title: Trastuzumab-induced HER reprogramming in “resistant” breast carcinoma cells publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-08-1056 contributor: fullname: Narayan – volume: 9 start-page: 463 year: 2009 ident: 2022061102283936300_bib2 article-title: Novel anticancer targets: revisiting ERBB2 and discovering ERBB3 publication-title: Nat Rev Cancer doi: 10.1038/nrc2656 contributor: fullname: Baselga – volume: 15 start-page: 2452 year: 1996 ident: 2022061102283936300_bib46 article-title: Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions publication-title: EMBO J doi: 10.1002/j.1460-2075.1996.tb00603.x contributor: fullname: Pinkas-Kramarski – volume: 18 start-page: 221 year: 2012 ident: 2022061102283936300_bib40 article-title: Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer publication-title: Nat Med doi: 10.1038/nm.2609 contributor: fullname: Montagut – volume: 11 start-page: 495 year: 2003 ident: 2022061102283936300_bib43 article-title: The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors publication-title: Mol Cell doi: 10.1016/S1097-2765(03)00048-0 contributor: fullname: Garrett – volume: 20 start-page: 423 year: 2011 ident: 2022061102283936300_bib10 article-title: Resistance to EGFR-targeted therapy: a family affair publication-title: Cancer Cell doi: 10.1016/j.ccr.2011.10.006 contributor: fullname: Vlacich – volume: 12 start-page: 323 year: 2012 ident: 2022061102283936300_bib18 article-title: Intra-tumour heterogeneity: a looking glass for cancer? publication-title: Nat Rev Cancer doi: 10.1038/nrc3261 contributor: fullname: Marusyk – volume: 84 start-page: 1105 year: 2012 ident: 2022061102283936300_bib9 article-title: Advances in bispecific biotherapeutics for the treatment of cancer publication-title: Biochem Pharmacol doi: 10.1016/j.bcp.2012.07.011 contributor: fullname: May – volume: 25 start-page: 1 year: 2011 ident: 2022061102283936300_bib49 article-title: Optimizing therapeutic antibody function: progress with Fc domain engineering publication-title: BioDrugs doi: 10.2165/11537830-000000000-00000 contributor: fullname: Kaneko – volume: 8 start-page: 277 year: 2013 ident: 2022061102283936300_bib19 article-title: Cellular heterogeneity and molecular evolution in cancer publication-title: Annu Rev Pathol doi: 10.1146/annurev-pathol-020712-163923 contributor: fullname: Almendro – volume: 55 start-page: 717 year: 2006 ident: 2022061102283936300_bib33 article-title: Humanization of a recombinant monoclonal antibody to produce a therapeutic HER dimerization inhibitor, pertuzumab publication-title: Cancer Immunol Immunother doi: 10.1007/s00262-005-0058-x contributor: fullname: Adams – volume: 110 start-page: 15389 year: 2013 ident: 2022061102283936300_bib38 article-title: Inhibition of pancreatic carcinoma by homo- and heterocombinations of antibodies against EGF-receptor and its kin HER2/ErbB-2 publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.1313857110 contributor: fullname: Maron – volume: 109 start-page: 3041 year: 2012 ident: 2022061102283936300_bib21 article-title: Intratumoral heterogeneity of receptor tyrosine kinases EGFR and PDGFRA amplification in glioblastoma defines subpopulations with distinct growth factor response publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.1114033109 contributor: fullname: Szerlip – volume: 5 start-page: 317 year: 2004 ident: 2022061102283936300_bib7 article-title: Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex publication-title: Cancer Cell doi: 10.1016/S1535-6108(04)00083-2 contributor: fullname: Franklin – volume: 358 start-page: 764 year: 2006 ident: 2022061102283936300_bib30 article-title: Isolation of human antibody repertoires with preservation of the natural heavy and light chain pairing publication-title: J Mol Biol doi: 10.1016/j.jmb.2006.02.040 contributor: fullname: Meijer – volume: 14 start-page: 121 year: 2012 ident: 2022061102283936300_bib36 article-title: In pancreatic carcinoma, dual EGFR/HER2 targeting with cetuximab/trastuzumab is more effective than treatment with trastuzumab/erlotinib or lapatinib alone: implication of receptors' down-regulation and dimers' disruption publication-title: Neoplasia doi: 10.1593/neo.111602 contributor: fullname: Larbouret |
SSID | ssj0014104 |
Score | 2.486056 |
Snippet | Accumulating evidence indicates a high degree of plasticity and compensatory signaling within the human epidermal growth factor receptor (HER) family, leading... Purpose: Accumulating evidence indicates a high degree of plasticity and compensatory signaling within the human epidermal growth factor receptor (HER) family,... PURPOSEAccumulating evidence indicates a high degree of plasticity and compensatory signaling within the human epidermal growth factor receptor (HER) family,... |
SourceID | proquest crossref pubmed |
SourceType | Aggregation Database Index Database |
StartPage | 4110 |
SubjectTerms | Animals Antibodies, Monoclonal, Humanized - chemistry Cell Line, Tumor Cell Proliferation Cell Survival Drug Resistance, Neoplasm - immunology ErbB Receptors - chemistry ErbB Receptors - immunology Gene Expression Regulation, Neoplastic Humans Ligands Mice Mice, Nude Neoplasms, Experimental - drug therapy Receptor, ErbB-2 - chemistry Receptor, ErbB-2 - immunology Receptor, ErbB-3 - chemistry Receptor, ErbB-3 - immunology Signal Transduction Xenograft Model Antitumor Assays |
Title | Pan-HER, an Antibody Mixture Simultaneously Targeting EGFR, HER2, and HER3, Effectively Overcomes Tumor Heterogeneity and Plasticity |
URI | https://www.ncbi.nlm.nih.gov/pubmed/25908781 https://search.proquest.com/docview/1713528455 https://search.proquest.com/docview/1808670469 |
Volume | 21 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lj9MwELbKIiEuiDflJSNxa1OSxk7s46rb0l22uytIpd4iJ3FFUUlQSSWWM2d-MzOOkzZiQQuXKE1qJ_J8Gc-MvxkT8lqEMlEuAzdVssxhjKeO5DpxwHbmAQuGjJtiOrOzYDpnJwu-6HR-7rGWtmUySL9fmVfyP1KFayBXzJL9B8k2ncIFOAf5whEkDMdryfhC5c60ojLAZ3qYl6ukyC57s9U3sy7wYYV0QZVr8O7Xl73IkL4xNDB-OzGNoO2wpm_CuW8UoyF4gA6EFucwIvDe-msv2n4uNjBHgRQKeB2NtrvJMwDjG3nZZWt1eFSnW6aIqU3PVhRqIs8noIYTG_qZ4srBbnHqotiu7Z2Ku7RjcR-pj2sbr8Wyz81U8UlVsDu2wQUbw_A4Ei6qLE6rdl2s88v8ll6uMqdr_Ik9Lcs8S4XV9meV2vz7bMCFCUzYzgej0XvHY47vW-Z2q_r22Xk8mZ-extF4Ed0gN7GwIu7FcHT8rlmVYp7ZjrLp0GaEwWPeXPmQtq3zBwfGGDLRXXLHeiD0sILTPdLR-X1ya2Y5Fg_ID4uqPlU5rTFFLaZoG1O0wRRFTPUpIgobZnjm9-kemmiDJmrQRFtoMm12aHpI5pNxNJo6dq8OJwWTt3SyMM0kVntU3NWJXPruEuZg-NglDzHSLqVSri8TLNeXepn0lPY5lgkJOHIgAv8ROciLXD8hNGBhJmDmCTXY6kN_CapECZeLTIQpGFqsSwb1qMZfqpIssXFluYhRDDGKIQYxgFsboxi65FU99jEoT1wRq4Yp9nCDSjDQOP_LfwR4_SGGkbrkcSW45rFDLl0RCu_pNVo_I7d30H9ODsrNVr8Ag7ZMXhqU_QId65i3 |
link.rule.ids | 314,780,784,27924,27925 |
linkProvider | Flying Publisher |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Pan-HER%2C+an+Antibody+Mixture+Simultaneously+Targeting+EGFR%2C+HER2%2C+and+HER3%2C+Effectively+Overcomes+Tumor+Heterogeneity+and+Plasticity&rft.jtitle=Clinical+cancer+research&rft.au=Jacobsen%2C+Helle+J&rft.au=Poulsen%2C+Thomas+T&rft.au=Dahlman%2C+Anna&rft.au=Kjaer%2C+Ida&rft.date=2015-09-15&rft.issn=1078-0432&rft.volume=21&rft.issue=18&rft.spage=4110&rft.epage=4122&rft_id=info:doi/10.1158%2F1078-0432.CCR-14-3312&rft.externalDBID=NO_FULL_TEXT |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1078-0432&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1078-0432&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1078-0432&client=summon |