HER2-HER3 Heterodimer Quantification by FRET-FLIM and Patient Subclass Analysis of the COIN Colorectal Trial
Abstract Background The phase III MRC COIN trial showed no statistically significant benefit from adding the EGFR-target cetuximab to oxaliplatin-based chemotherapy in first-line treatment of advanced colorectal cancer. This study exploits additional information on HER2-HER3 dimerization to achieve...
Saved in:
| Published in: | JNCI : Journal of the National Cancer Institute Vol. 112; no. 9; pp. 944 - 954 |
|---|---|
| Main Authors: | , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
Oxford University Press
01.09.2020
|
| Subjects: | |
| ISSN: | 0027-8874, 1460-2105, 1460-2105 |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Abstract | Abstract
Background
The phase III MRC COIN trial showed no statistically significant benefit from adding the EGFR-target cetuximab to oxaliplatin-based chemotherapy in first-line treatment of advanced colorectal cancer. This study exploits additional information on HER2-HER3 dimerization to achieve patient stratification and reveal previously hidden subgroups of patients who had differing disease progression and treatment response.
Methods
HER2-HER3 dimerization was quantified by fluorescence lifetime imaging microscopy in primary tumor samples from 550 COIN trial patients receiving oxaliplatin and fluoropyrimidine chemotherapy with or without cetuximab. Bayesian latent class analysis and covariate reduction was performed to analyze the effects of HER2-HER3 dimer, RAS mutation, and cetuximab on progression-free survival and overall survival (OS). All statistical tests were two-sided.
Results
Latent class analysis on a cohort of 398 patients revealed two patient subclasses with differing prognoses (median OS = 1624 days [95% confidence interval [CI] = 1466 to 1816 days] vs 461 days [95% CI = 431 to 504 days]): Class 1 (15.6%) showed a benefit from cetuximab in OS (hazard ratio = 0.43, 95% CI = 0.25 to 0.76, P = .004). Class 2 showed an association of increased HER2-HER3 with better OS (hazard ratio = 0.64, 95% CI = 0.44 to 0.94, P = .02). A class prediction signature was formed and tested on an independent validation cohort (n = 152) validating the prognostic utility of the dimer assay. Similar subclasses were also discovered in full trial dataset (n = 1630) based on 10 baseline clinicopathological and genetic covariates.
Conclusions
Our work suggests that the combined use of HER dimer imaging and conventional mutation analyses will be able to identify a small subclass of patients (>10%) who will have better prognosis following chemotherapy. A larger prospective cohort will be required to confirm its utility in predicting the outcome of anti-EGFR treatment. |
|---|---|
| AbstractList | The phase III MRC COIN trial showed no statistically significant benefit from adding the EGFR-target cetuximab to oxaliplatin-based chemotherapy in first-line treatment of advanced colorectal cancer. This study exploits additional information on HER2-HER3 dimerization to achieve patient stratification and reveal previously hidden subgroups of patients who had differing disease progression and treatment response.BACKGROUNDThe phase III MRC COIN trial showed no statistically significant benefit from adding the EGFR-target cetuximab to oxaliplatin-based chemotherapy in first-line treatment of advanced colorectal cancer. This study exploits additional information on HER2-HER3 dimerization to achieve patient stratification and reveal previously hidden subgroups of patients who had differing disease progression and treatment response.HER2-HER3 dimerization was quantified by fluorescence lifetime imaging microscopy in primary tumor samples from 550 COIN trial patients receiving oxaliplatin and fluoropyrimidine chemotherapy with or without cetuximab. Bayesian latent class analysis and covariate reduction was performed to analyze the effects of HER2-HER3 dimer, RAS mutation, and cetuximab on progression-free survival and overall survival (OS). All statistical tests were two-sided.METHODSHER2-HER3 dimerization was quantified by fluorescence lifetime imaging microscopy in primary tumor samples from 550 COIN trial patients receiving oxaliplatin and fluoropyrimidine chemotherapy with or without cetuximab. Bayesian latent class analysis and covariate reduction was performed to analyze the effects of HER2-HER3 dimer, RAS mutation, and cetuximab on progression-free survival and overall survival (OS). All statistical tests were two-sided.Latent class analysis on a cohort of 398 patients revealed two patient subclasses with differing prognoses (median OS = 1624 days [95% confidence interval [CI] = 1466 to 1816 days] vs 461 days [95% CI = 431 to 504 days]): Class 1 (15.6%) showed a benefit from cetuximab in OS (hazard ratio = 0.43, 95% CI = 0.25 to 0.76, P = .004). Class 2 showed an association of increased HER2-HER3 with better OS (hazard ratio = 0.64, 95% CI = 0.44 to 0.94, P = .02). A class prediction signature was formed and tested on an independent validation cohort (n = 152) validating the prognostic utility of the dimer assay. Similar subclasses were also discovered in full trial dataset (n = 1630) based on 10 baseline clinicopathological and genetic covariates.RESULTSLatent class analysis on a cohort of 398 patients revealed two patient subclasses with differing prognoses (median OS = 1624 days [95% confidence interval [CI] = 1466 to 1816 days] vs 461 days [95% CI = 431 to 504 days]): Class 1 (15.6%) showed a benefit from cetuximab in OS (hazard ratio = 0.43, 95% CI = 0.25 to 0.76, P = .004). Class 2 showed an association of increased HER2-HER3 with better OS (hazard ratio = 0.64, 95% CI = 0.44 to 0.94, P = .02). A class prediction signature was formed and tested on an independent validation cohort (n = 152) validating the prognostic utility of the dimer assay. Similar subclasses were also discovered in full trial dataset (n = 1630) based on 10 baseline clinicopathological and genetic covariates.Our work suggests that the combined use of HER dimer imaging and conventional mutation analyses will be able to identify a small subclass of patients (>10%) who will have better prognosis following chemotherapy. A larger prospective cohort will be required to confirm its utility in predicting the outcome of anti-EGFR treatment.CONCLUSIONSOur work suggests that the combined use of HER dimer imaging and conventional mutation analyses will be able to identify a small subclass of patients (>10%) who will have better prognosis following chemotherapy. A larger prospective cohort will be required to confirm its utility in predicting the outcome of anti-EGFR treatment. The phase III MRC COIN trial showed no statistically significant benefit from adding the EGFR-target cetuximab to oxaliplatin-based chemotherapy in first-line treatment of advanced colorectal cancer. This study exploits additional information on HER2-HER3 dimerization to achieve patient stratification and reveal previously hidden subgroups of patients who had differing disease progression and treatment response. HER2-HER3 dimerization was quantified by fluorescence lifetime imaging microscopy in primary tumor samples from 550 COIN trial patients receiving oxaliplatin and fluoropyrimidine chemotherapy with or without cetuximab. Bayesian latent class analysis and covariate reduction was performed to analyze the effects of HER2-HER3 dimer, RAS mutation, and cetuximab on progression-free survival and overall survival (OS). All statistical tests were two-sided. Latent class analysis on a cohort of 398 patients revealed two patient subclasses with differing prognoses (median OS = 1624 days [95% confidence interval [CI] = 1466 to 1816 days] vs 461 days [95% CI = 431 to 504 days]): Class 1 (15.6%) showed a benefit from cetuximab in OS (hazard ratio = 0.43, 95% CI = 0.25 to 0.76, P = .004). Class 2 showed an association of increased HER2-HER3 with better OS (hazard ratio = 0.64, 95% CI = 0.44 to 0.94, P = .02). A class prediction signature was formed and tested on an independent validation cohort (n = 152) validating the prognostic utility of the dimer assay. Similar subclasses were also discovered in full trial dataset (n = 1630) based on 10 baseline clinicopathological and genetic covariates. Our work suggests that the combined use of HER dimer imaging and conventional mutation analyses will be able to identify a small subclass of patients (>10%) who will have better prognosis following chemotherapy. A larger prospective cohort will be required to confirm its utility in predicting the outcome of anti-EGFR treatment. Abstract Background The phase III MRC COIN trial showed no statistically significant benefit from adding the EGFR-target cetuximab to oxaliplatin-based chemotherapy in first-line treatment of advanced colorectal cancer. This study exploits additional information on HER2-HER3 dimerization to achieve patient stratification and reveal previously hidden subgroups of patients who had differing disease progression and treatment response. Methods HER2-HER3 dimerization was quantified by fluorescence lifetime imaging microscopy in primary tumor samples from 550 COIN trial patients receiving oxaliplatin and fluoropyrimidine chemotherapy with or without cetuximab. Bayesian latent class analysis and covariate reduction was performed to analyze the effects of HER2-HER3 dimer, RAS mutation, and cetuximab on progression-free survival and overall survival (OS). All statistical tests were two-sided. Results Latent class analysis on a cohort of 398 patients revealed two patient subclasses with differing prognoses (median OS = 1624 days [95% confidence interval [CI] = 1466 to 1816 days] vs 461 days [95% CI = 431 to 504 days]): Class 1 (15.6%) showed a benefit from cetuximab in OS (hazard ratio = 0.43, 95% CI = 0.25 to 0.76, P = .004). Class 2 showed an association of increased HER2-HER3 with better OS (hazard ratio = 0.64, 95% CI = 0.44 to 0.94, P = .02). A class prediction signature was formed and tested on an independent validation cohort (n = 152) validating the prognostic utility of the dimer assay. Similar subclasses were also discovered in full trial dataset (n = 1630) based on 10 baseline clinicopathological and genetic covariates. Conclusions Our work suggests that the combined use of HER dimer imaging and conventional mutation analyses will be able to identify a small subclass of patients (>10%) who will have better prognosis following chemotherapy. A larger prospective cohort will be required to confirm its utility in predicting the outcome of anti-EGFR treatment. |
| Author | Kaplan, Richard Maughan, Timothy S. Lawler, Katherine Brown, Louise Rodriguez-Justo, Manuel Coolen, Anthony C C Barrett, James E Hochhauser, Daniel Gao, Fangfei Ng, Tony Weitsman, Gregory Barber, Paul R Deng, Jinhai Fisher, David Vojnovic, Borivoj Adams, Richard Tullis, Iain D C Rowley, Mark |
| Author_xml | – sequence: 1 givenname: Paul R orcidid: 0000-0002-8595-1141 surname: Barber fullname: Barber, Paul R organization: UCL Cancer Institute, Paul O’Gorman Building, University College London, London, UK – sequence: 2 givenname: Gregory surname: Weitsman fullname: Weitsman, Gregory organization: Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King’s College London, London, UK – sequence: 3 givenname: Katherine surname: Lawler fullname: Lawler, Katherine organization: Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King’s College London, London, UK – sequence: 4 givenname: James E surname: Barrett fullname: Barrett, James E organization: Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King’s College London, London, UK – sequence: 5 givenname: Mark surname: Rowley fullname: Rowley, Mark organization: Institute for Mathematical and Molecular Biomedicine, King’s College London, Guy’s Medical School Campus, London, UK – sequence: 6 givenname: Manuel orcidid: 0000-0001-5007-1761 surname: Rodriguez-Justo fullname: Rodriguez-Justo, Manuel organization: UCL Cancer Institute, Paul O’Gorman Building, University College London, London, UK – sequence: 7 givenname: David orcidid: 0000-0002-2512-2296 surname: Fisher fullname: Fisher, David organization: MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London, UK – sequence: 8 givenname: Fangfei surname: Gao fullname: Gao, Fangfei organization: UCL Cancer Institute, Paul O’Gorman Building, University College London, London, UK – sequence: 9 givenname: Iain D C orcidid: 0000-0001-5148-0161 surname: Tullis fullname: Tullis, Iain D C organization: Department of Oncology, Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK – sequence: 10 givenname: Jinhai surname: Deng fullname: Deng, Jinhai organization: Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King’s College London, London, UK – sequence: 11 givenname: Louise orcidid: 0000-0003-2827-6634 surname: Brown fullname: Brown, Louise organization: MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London, UK – sequence: 12 givenname: Richard orcidid: 0000-0002-0189-8348 surname: Kaplan fullname: Kaplan, Richard organization: MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London, UK – sequence: 13 givenname: Daniel surname: Hochhauser fullname: Hochhauser, Daniel organization: UCL Cancer Institute, Paul O’Gorman Building, University College London, London, UK – sequence: 14 givenname: Richard orcidid: 0000-0003-3915-7243 surname: Adams fullname: Adams, Richard organization: School of Medicine, Cardiff University, Cardiff, UK – sequence: 15 givenname: Timothy S. surname: Maughan fullname: Maughan, Timothy S. organization: Department of Oncology, Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK – sequence: 16 givenname: Borivoj surname: Vojnovic fullname: Vojnovic, Borivoj organization: Department of Oncology, Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK – sequence: 17 givenname: Anthony C C surname: Coolen fullname: Coolen, Anthony C C organization: Institute for Mathematical and Molecular Biomedicine, King’s College London, Guy’s Medical School Campus, London, UK – sequence: 18 givenname: Tony surname: Ng fullname: Ng, Tony email: tony.ng@kcl.ac.uk organization: UCL Cancer Institute, Paul O’Gorman Building, University College London, London, UK |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31851321$$D View this record in MEDLINE/PubMed |
| BookMark | eNo9kDtPwzAURi0Eog-Y2JEnxBLqVx4eq6illQqFUubIcRzhyrFL7Azl15OqhTt8V7r36BvOCFxaZxUAdxg9YcTpZGelnlS7H0LxBRhilqCIYBRfgiFCJI2yLGUDMPJ-h_rhhF2DAcVZjCnBQ2AWsw2J-qBwoYJqXaUb1cL3Ttigay1F0M7C8gDnm9k2mq-WL1DYCr71d2UD_OhKaYT3cGqFOXjtoath-FIwXy9fYe6Ma5UMwsBtq4W5AVe1MF7dnvcYfM5n23wRrdbPy3y6iiRjKERVTVIuOS0ZR4plFSeScUY5lSnNUJ1QnqaUJCIjcZrwksVIVbVCleASYylSOgaPp95967475UPRaC-VMcIq1_mCUJJRxpPe3hjcn9GubFRV7FvdiPZQ_BnqgYcT4Lr9_xej4qi-OKovTurpL99EdGA |
| CitedBy_id | crossref_primary_10_1016_j_bpc_2022_106768 crossref_primary_10_1186_s12885_023_11600_z crossref_primary_10_1038_s41419_022_04709_9 crossref_primary_10_7554_eLife_73288 crossref_primary_10_1038_s41416_022_02015_x crossref_primary_10_1016_j_actbio_2021_08_055 |
| ContentType | Journal Article |
| Copyright | The Author(s) 2019. Published by Oxford University Press. 2019 The Author(s) 2019. Published by Oxford University Press. |
| Copyright_xml | – notice: The Author(s) 2019. Published by Oxford University Press. 2019 – notice: The Author(s) 2019. Published by Oxford University Press. |
| DBID | TOX CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1093/jnci/djz231 |
| DatabaseName | Oxford Journals Open Access Collection Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: TOX name: Oxford Journals Open Access Collection url: https://academic.oup.com/journals/ sourceTypes: Publisher – sequence: 3 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1460-2105 |
| EndPage | 954 |
| ExternalDocumentID | 31851321 10.1093/jnci/djz231 |
| Genre | Validation Study Research Support, Non-U.S. Gov't Journal Article |
| GrantInformation_xml | – fundername: Medical Research Council grantid: MR/M016587/1 – fundername: Cancer Research UK grantid: C7893/A26233 – fundername: Cancer Research UK grantid: 25350 – fundername: Cancer Research UK grantid: 16463 – fundername: Medical Research Council grantid: G0701770 – fundername: Department of Health grantid: 11/100/50 – fundername: Medical Research Council grantid: MC_UU_12023/25 – fundername: Medical Research Council grantid: MC_UU_12023/20 – fundername: Cancer Research UK grantid: 26553 – fundername: Cancer Research UK grantid: C1519/A10331 |
| GroupedDBID | --- -DD -E4 -~X .2P .55 .GJ .I3 .XZ .ZR 08P 0R~ 186 1TH 29L 2QL 2WC 354 3O- 4.4 482 48X 53G 5GY 5RE 5VS 5WD 6.Y 70D 8WZ 96U A6W AABZA AACZT AAGKA AAHTB AAJKP AAJQQ AAKAS AAMVS AAOGV AAPGJ AAPNW AAPQZ AAPXW AAQQT AARHZ AASNB AAUAY AAUQX AAVAP AAWDT AAWTL ABCQX ABEFU ABEUO ABIXL ABJNI ABKDP ABNHQ ABNKS ABOCM ABPEJ ABPMR ABPPZ ABPTD ABQLI ABQNK ABQTQ ABSAR ABSMQ ABXVV ABZBJ ACBMB ACFRR ACGFO ACGFS ACGOD ACKOT ACMRT ACNCT ACPQN ACPRK ACUFI ACUTJ ACUTO ACYHN ACZBC ADBBV ADEYI ADEZT ADGZP ADHKW ADHZD ADIPN ADJQC ADOCK ADQBN ADRIX ADRTK ADVEK ADYVW ADZCM ADZXQ AEGPL AEJOX AEKPW AEKSI AEMDU AENZO AEPUE AETBJ AETEA AEWNT AFAZI AFCHL AFFNX AFFZL AFIYH AFOFC AFRAH AFSHK AFXAL AFYAG AGINJ AGKEF AGKRT AGMDO AGNAY AGSYK AGUTN AHMBA AHXPO AI. AIAGR AIJHB AJEEA ALMA_UNASSIGNED_HOLDINGS ALUQC APIBT APJGH APWMN AQDSO AQKUS ASPBG ATGXG ATTQO AVNTJ AVWKF AZFZN BAWUL BAYMD BCRHZ BEYMZ BKOMP BTRTY BVRKM BZKNY C45 CAG CDBKE COF CS3 CZ4 DAKXR DIK DILTD DU5 D~K E3Z EBS EE~ EIHJH EJD EMOBN ENERS F3I F5P F8P F9B FA8 FECEO FEDTE FLUFQ FOEOM FOTVD FQBLK GAUVT GJXCC GOZPB GRPMH GX1 H13 H5~ HAR HVGLF HW0 HZ~ IH2 IOX J21 J5H JXSIZ KAQDR KBUDW KC5 KOP KQ8 KSI KSN L7B LXL LXN LXY M-Z M49 MBLQV MHKGH ML0 MVM N9A NGC NOMLY NOYVH NTWIH NU- NVLIB O0~ OAUYM OAWHX OBH OCB OCZFY ODMLO ODZKP OGEVE OHH OJQWA OJZSN OK1 OPAEJ OVD OWPYF O~Y P2P PAFKI PB- PEELM PQQKQ Q.- Q1. Q5Y QBD R44 RD5 RHF RNI RNS ROL ROX ROZ RUSNO RW1 RXO RZF RZO TCURE TEORI TJX TMA TOX TR2 TWZ UDS UPT VH1 VVN W8F WH7 WOQ X7H X7M XJT Y6R YAYTL YHZ YKOAZ YQT YXANX ZKX ZRR ZY1 ~91 ~H1 ~X8 ABDFA ABEJV ABGNP ABVGC ADNBA AEMQT AGORE AHGBF AHMMS AJBYB AJNCP ALXQX CGR CUY CVF ECM EIF NPM 7X8 |
| ID | FETCH-LOGICAL-c440t-df279c93b490e48d92c494393c7380f63977326a825769b450edfe0da9c11ca73 |
| IEDL.DBID | TOX |
| ISICitedReferencesCount | 9 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000593054300013&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 0027-8874 1460-2105 |
| IngestDate | Sun Sep 28 09:16:21 EDT 2025 Mon Jul 21 06:05:04 EDT 2025 Wed Aug 28 03:18:35 EDT 2024 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 9 |
| Language | English |
| License | This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. The Author(s) 2019. Published by Oxford University Press. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c440t-df279c93b490e48d92c494393c7380f63977326a825769b450edfe0da9c11ca73 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 |
| ORCID | 0000-0003-2827-6634 0000-0002-0189-8348 0000-0002-8595-1141 0000-0001-5007-1761 0000-0001-5148-0161 0000-0002-2512-2296 0000-0003-3915-7243 |
| OpenAccessLink | https://dx.doi.org/10.1093/jnci/djz231 |
| PMID | 31851321 |
| PQID | 2328349609 |
| PQPubID | 23479 |
| PageCount | 11 |
| ParticipantIDs | proquest_miscellaneous_2328349609 pubmed_primary_31851321 oup_primary_10_1093_jnci_djz231 |
| PublicationCentury | 2000 |
| PublicationDate | 2020-09-01 |
| PublicationDateYYYYMMDD | 2020-09-01 |
| PublicationDate_xml | – month: 09 year: 2020 text: 2020-09-01 day: 01 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | JNCI : Journal of the National Cancer Institute |
| PublicationTitleAlternate | J Natl Cancer Inst |
| PublicationYear | 2020 |
| Publisher | Oxford University Press |
| Publisher_xml | – name: Oxford University Press |
| SSID | ssj0000924 |
| Score | 2.4059694 |
| Snippet | Abstract
Background
The phase III MRC COIN trial showed no statistically significant benefit from adding the EGFR-target cetuximab to oxaliplatin-based... The phase III MRC COIN trial showed no statistically significant benefit from adding the EGFR-target cetuximab to oxaliplatin-based chemotherapy in first-line... |
| SourceID | proquest pubmed oup |
| SourceType | Aggregation Database Index Database Publisher |
| StartPage | 944 |
| SubjectTerms | Adenocarcinoma - diagnosis Adenocarcinoma - metabolism Adenocarcinoma - mortality Adenocarcinoma - therapy Aged Antineoplastic Combined Chemotherapy Protocols - therapeutic use Bayes Theorem Capecitabine - therapeutic use Cohort Studies Colorectal Neoplasms - diagnosis Colorectal Neoplasms - metabolism Colorectal Neoplasms - mortality Colorectal Neoplasms - therapy Female Fluorescence Resonance Energy Transfer Humans Latent Class Analysis Male Microscopy - methods Middle Aged Oxaloacetates - therapeutic use Prognosis Protein Multimerization Randomized Controlled Trials as Topic - statistics & numerical data Receptor, ErbB-2 - analysis Receptor, ErbB-2 - metabolism Receptor, ErbB-3 - analysis Receptor, ErbB-3 - metabolism Tissue Array Analysis Treatment Outcome |
| Title | HER2-HER3 Heterodimer Quantification by FRET-FLIM and Patient Subclass Analysis of the COIN Colorectal Trial |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/31851321 https://www.proquest.com/docview/2328349609 |
| Volume | 112 |
| WOSCitedRecordID | wos000593054300013&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1LSwMxEA5aRLz4ftRHjeB1aXaT3SRHKS310IelQm_L5rFQ0V3pQ9Bf72R3q1AFveSWECaTL98wM18QuuWpcA2c1DNRpD3GlfZUFMLFS2XiG0MhImDFZxO83xeTiRxWBbLzX1L4kjafMj1tmqePoGiX9kPh3Hk8mHwDrgwqsWUAXMFZ1Ya3Nnetg-0HkSwelM7ef7eyj3YryojvyjM-QBs2O0TbvSopfoSeu-1R4MFAcdcVt-Rm-mJn-GGZlIVAhe2xesedUXvsdQCucJIZPCwVVTFAh3YUGq_0SXCeYqCFuDW47-MWgKMDRdjA2PnqMXrstMetrld9ouBpxsjCM2nApZZUMUksE0YGmklgIVRzKkjq8nocKFwiXOQhFQuJNaklJpHa93XC6QmqZXlmzxAOU1qI2QBloSwhkYqoDZQACiW1UoTX0TVYOH4tZTLiMr1NY2e0uDRaHd2srB-DG7vcRJLZfDmPgdgJp11PZB2dlsfytZBr8Iag2T__c_0LtBO4eLioAbtEtcVsaa_Qln5bTOezBtrkEwFjf9hrFB70CV9yvVc |
| linkProvider | Oxford University Press |
| 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=HER2-HER3+Heterodimer+Quantification+by+FRET-FLIM+and+Patient+Subclass+Analysis+of+the+COIN+Colorectal+Trial&rft.jtitle=JNCI+%3A+Journal+of+the+National+Cancer+Institute&rft.au=Barber%2C+Paul+R&rft.au=Weitsman%2C+Gregory&rft.au=Lawler%2C+Katherine&rft.au=Barrett%2C+James+E&rft.date=2020-09-01&rft.pub=Oxford+University+Press&rft.issn=0027-8874&rft.eissn=1460-2105&rft.volume=112&rft.issue=9&rft.spage=944&rft.epage=954&rft_id=info:doi/10.1093%2Fjnci%2Fdjz231&rft.externalDocID=10.1093%2Fjnci%2Fdjz231 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0027-8874&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0027-8874&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0027-8874&client=summon |