Discovery of a putative blood-based protein signature associated with response to ALK tyrosine kinase inhibition
ALK tyrosine kinase inhibition has become a mainstay in the clinical management of ALK fusion positive NSCLC patients. Although ALK mutations can reliably predict the likelihood of response to ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, they cannot reliably predict response duration or...
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| Veröffentlicht in: | Clinical proteomics 2020-02, Vol.17 (1), p.5-5, Article 5 |
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| creator | Couëtoux du Tertre, Mathilde Marques, Maud McNamara, Suzan Gambaro, Karen Hoffert, Cyrla Tremblay, Lise Bouchard, Nicole Diaconescu, Razvan Blais, Normand Couture, Christian Pelsser, Vincent Wang, Hangjun McIntosh, Laura Hindie, Valérie Parent, Stephane Cortes, Laetitia Breton, Yannick-André Pottiez, Gwenael Croteau, Pascal Higenell, Valerie Izzi, Luisa Spatz, Alan Cohen, Victor Batist, Gerald Agulnik, Jason |
| description | ALK tyrosine kinase inhibition has become a mainstay in the clinical management of ALK fusion positive NSCLC patients. Although ALK mutations can reliably predict the likelihood of response to ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, they cannot reliably predict response duration or intrinsic/extrinsic therapeutic resistance. To further refine the application of personalized medicine in this indication, this study aimed to identify prognostic proteomic biomarkers in ALK fusion positive NSCLC patients to crizotinib.
Twenty-four patients with advanced NSCLC harboring ALK fusion were administered crizotinib in a phase IV trial which included blood sampling prior to treatment. Targeted proteomics of 327 proteins using MRM-MS was used to measure plasma levels at baseline (including pre-treatment and early treatment blood samples) and assess potential clinical association.
Patients were categorized by duration of response: long-term responders [PFS ≥ 24 months (n = 7)], normal responders [3 |
| doi_str_mv | 10.1186/s12014-020-9269-6 |
| format | Article |
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Twenty-four patients with advanced NSCLC harboring ALK fusion were administered crizotinib in a phase IV trial which included blood sampling prior to treatment. Targeted proteomics of 327 proteins using MRM-MS was used to measure plasma levels at baseline (including pre-treatment and early treatment blood samples) and assess potential clinical association.
Patients were categorized by duration of response: long-term responders [PFS ≥ 24 months (n = 7)], normal responders [3 < PFS < 24 months (n = 10)] and poor responders [PFS ≤ 3 months (n = 5)]. Several proteins were identified as differentially expressed between long-term responders and poor responders, including DPP4, KIT and LUM. Next, using machine learning algorithms, we evaluated the classification potential of 40 proteins. Finally, by integrating the different analytic methods, we selected 22 proteins as potential candidates for a blood-based prognostic signature of response to crizotinib in NSCLC patients harboring ALK fusion.
In conjunction with ALK mutation, the expression of this proteomic signature may represent a liquid biopsy-based marker of long-term response to crizotinib in NSCLC. Expanding the utility of prognostic biomarkers of response duration could influence choice of therapy, therapeutic sequencing, and potentially the need for alternative or combination therapy.
ClinicalTrials.gov, NCT02041468. Registered 22 January 2014, https://clinicaltrials.gov/ct2/show/NCT02041468?term=NCT02041468&rank=1.</description><identifier>ISSN: 1542-6416</identifier><identifier>EISSN: 1559-0275</identifier><identifier>DOI: 10.1186/s12014-020-9269-6</identifier><identifier>PMID: 32055239</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Algorithms ; Amino acids ; Biological markers ; Blood tests ; Clinical trials ; Crizotinib ; Data mining ; Health aspects ; Lung cancer ; Machine learning ; Non-small cell lung cancer ; Phenols (Class of compounds) ; Precision medicine ; Proteins ; Proteomics ; Tyrosine</subject><ispartof>Clinical proteomics, 2020-02, Vol.17 (1), p.5-5, Article 5</ispartof><rights>The Author(s) 2020.</rights><rights>COPYRIGHT 2020 BioMed Central Ltd.</rights><rights>The Author(s) 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c497t-f1ac4eb000e75a48badfb8cabfd1b6d2d16d9ab07322d336e00351b3a1b846bc3</citedby><cites>FETCH-LOGICAL-c497t-f1ac4eb000e75a48badfb8cabfd1b6d2d16d9ab07322d336e00351b3a1b846bc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006423/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006423/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32055239$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Couëtoux du Tertre, Mathilde</creatorcontrib><creatorcontrib>Marques, Maud</creatorcontrib><creatorcontrib>McNamara, Suzan</creatorcontrib><creatorcontrib>Gambaro, Karen</creatorcontrib><creatorcontrib>Hoffert, Cyrla</creatorcontrib><creatorcontrib>Tremblay, Lise</creatorcontrib><creatorcontrib>Bouchard, Nicole</creatorcontrib><creatorcontrib>Diaconescu, Razvan</creatorcontrib><creatorcontrib>Blais, Normand</creatorcontrib><creatorcontrib>Couture, Christian</creatorcontrib><creatorcontrib>Pelsser, Vincent</creatorcontrib><creatorcontrib>Wang, Hangjun</creatorcontrib><creatorcontrib>McIntosh, Laura</creatorcontrib><creatorcontrib>Hindie, Valérie</creatorcontrib><creatorcontrib>Parent, Stephane</creatorcontrib><creatorcontrib>Cortes, Laetitia</creatorcontrib><creatorcontrib>Breton, Yannick-André</creatorcontrib><creatorcontrib>Pottiez, Gwenael</creatorcontrib><creatorcontrib>Croteau, Pascal</creatorcontrib><creatorcontrib>Higenell, Valerie</creatorcontrib><creatorcontrib>Izzi, Luisa</creatorcontrib><creatorcontrib>Spatz, Alan</creatorcontrib><creatorcontrib>Cohen, Victor</creatorcontrib><creatorcontrib>Batist, Gerald</creatorcontrib><creatorcontrib>Agulnik, Jason</creatorcontrib><title>Discovery of a putative blood-based protein signature associated with response to ALK tyrosine kinase inhibition</title><title>Clinical proteomics</title><addtitle>Clin Proteomics</addtitle><description>ALK tyrosine kinase inhibition has become a mainstay in the clinical management of ALK fusion positive NSCLC patients. Although ALK mutations can reliably predict the likelihood of response to ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, they cannot reliably predict response duration or intrinsic/extrinsic therapeutic resistance. To further refine the application of personalized medicine in this indication, this study aimed to identify prognostic proteomic biomarkers in ALK fusion positive NSCLC patients to crizotinib.
Twenty-four patients with advanced NSCLC harboring ALK fusion were administered crizotinib in a phase IV trial which included blood sampling prior to treatment. Targeted proteomics of 327 proteins using MRM-MS was used to measure plasma levels at baseline (including pre-treatment and early treatment blood samples) and assess potential clinical association.
Patients were categorized by duration of response: long-term responders [PFS ≥ 24 months (n = 7)], normal responders [3 < PFS < 24 months (n = 10)] and poor responders [PFS ≤ 3 months (n = 5)]. Several proteins were identified as differentially expressed between long-term responders and poor responders, including DPP4, KIT and LUM. Next, using machine learning algorithms, we evaluated the classification potential of 40 proteins. Finally, by integrating the different analytic methods, we selected 22 proteins as potential candidates for a blood-based prognostic signature of response to crizotinib in NSCLC patients harboring ALK fusion.
In conjunction with ALK mutation, the expression of this proteomic signature may represent a liquid biopsy-based marker of long-term response to crizotinib in NSCLC. Expanding the utility of prognostic biomarkers of response duration could influence choice of therapy, therapeutic sequencing, and potentially the need for alternative or combination therapy.
ClinicalTrials.gov, NCT02041468. Registered 22 January 2014, https://clinicaltrials.gov/ct2/show/NCT02041468?term=NCT02041468&rank=1.</description><subject>Algorithms</subject><subject>Amino acids</subject><subject>Biological markers</subject><subject>Blood tests</subject><subject>Clinical trials</subject><subject>Crizotinib</subject><subject>Data mining</subject><subject>Health aspects</subject><subject>Lung cancer</subject><subject>Machine learning</subject><subject>Non-small cell lung cancer</subject><subject>Phenols (Class of compounds)</subject><subject>Precision medicine</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Tyrosine</subject><issn>1542-6416</issn><issn>1559-0275</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNptkkuLFDEUhYMozkzrD3AjAWGYTY15VapqIzTjExvc6Drkcas7Wp2UlVRL_3tT9DhMg2SRcPOdQ3I4CL2i5JbSVr5NlBEqKsJI1THZVfIJuqR13ZVJUz9dzoJVUlB5ga5S-kkI60TXPkcXnJG6Zry7RON7n2w8wHTEsccaj3PW2R8AmyFGVxmdwOFxihl8wMlvg87zBFinFK3XuVz-8XmHJ0hjDAlwjni9-YrzcYrJB8C_fCgW2IedNz77GF6gZ70eEry831fox8cP3-8-V5tvn77crTeVFV2Tq55qK8AQQqCptWiNdr1prTa9o0Y65qh0nTak4Yw5ziUQwmtquKamFdJYvkLvTr7jbPbgLIQ86UGNk9_r6aii9ur8Jvid2saDagiRgvFicHNvMMXfM6Ss9iUqGAYdIM5JMV6SFqQuT1ihNyd0qwdQPvSxONoFV2tJixtrm7pQt_-hynKw9zYG6H2ZnwmuHwl2oIe8S3GYlxjTOUhPoC2ppwn6h29SopamqFNTVGmKWpqiZNG8fpzPg-JfNfhfIHW7Cg</recordid><startdate>20200207</startdate><enddate>20200207</enddate><creator>Couëtoux du Tertre, Mathilde</creator><creator>Marques, Maud</creator><creator>McNamara, Suzan</creator><creator>Gambaro, Karen</creator><creator>Hoffert, Cyrla</creator><creator>Tremblay, Lise</creator><creator>Bouchard, Nicole</creator><creator>Diaconescu, Razvan</creator><creator>Blais, Normand</creator><creator>Couture, Christian</creator><creator>Pelsser, Vincent</creator><creator>Wang, Hangjun</creator><creator>McIntosh, Laura</creator><creator>Hindie, Valérie</creator><creator>Parent, Stephane</creator><creator>Cortes, Laetitia</creator><creator>Breton, Yannick-André</creator><creator>Pottiez, Gwenael</creator><creator>Croteau, Pascal</creator><creator>Higenell, Valerie</creator><creator>Izzi, Luisa</creator><creator>Spatz, Alan</creator><creator>Cohen, Victor</creator><creator>Batist, Gerald</creator><creator>Agulnik, Jason</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200207</creationdate><title>Discovery of a putative blood-based protein signature associated with response to ALK tyrosine kinase inhibition</title><author>Couëtoux du Tertre, Mathilde ; Marques, Maud ; McNamara, Suzan ; Gambaro, Karen ; Hoffert, Cyrla ; Tremblay, Lise ; Bouchard, Nicole ; Diaconescu, Razvan ; Blais, Normand ; Couture, Christian ; Pelsser, Vincent ; Wang, Hangjun ; McIntosh, Laura ; Hindie, Valérie ; Parent, Stephane ; Cortes, Laetitia ; Breton, Yannick-André ; Pottiez, Gwenael ; Croteau, Pascal ; Higenell, Valerie ; Izzi, Luisa ; Spatz, Alan ; Cohen, Victor ; Batist, Gerald ; Agulnik, Jason</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c497t-f1ac4eb000e75a48badfb8cabfd1b6d2d16d9ab07322d336e00351b3a1b846bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Algorithms</topic><topic>Amino acids</topic><topic>Biological markers</topic><topic>Blood tests</topic><topic>Clinical trials</topic><topic>Crizotinib</topic><topic>Data mining</topic><topic>Health aspects</topic><topic>Lung cancer</topic><topic>Machine learning</topic><topic>Non-small cell lung cancer</topic><topic>Phenols (Class of compounds)</topic><topic>Precision medicine</topic><topic>Proteins</topic><topic>Proteomics</topic><topic>Tyrosine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Couëtoux du Tertre, Mathilde</creatorcontrib><creatorcontrib>Marques, Maud</creatorcontrib><creatorcontrib>McNamara, Suzan</creatorcontrib><creatorcontrib>Gambaro, Karen</creatorcontrib><creatorcontrib>Hoffert, Cyrla</creatorcontrib><creatorcontrib>Tremblay, Lise</creatorcontrib><creatorcontrib>Bouchard, Nicole</creatorcontrib><creatorcontrib>Diaconescu, Razvan</creatorcontrib><creatorcontrib>Blais, Normand</creatorcontrib><creatorcontrib>Couture, Christian</creatorcontrib><creatorcontrib>Pelsser, Vincent</creatorcontrib><creatorcontrib>Wang, Hangjun</creatorcontrib><creatorcontrib>McIntosh, Laura</creatorcontrib><creatorcontrib>Hindie, Valérie</creatorcontrib><creatorcontrib>Parent, Stephane</creatorcontrib><creatorcontrib>Cortes, Laetitia</creatorcontrib><creatorcontrib>Breton, Yannick-André</creatorcontrib><creatorcontrib>Pottiez, Gwenael</creatorcontrib><creatorcontrib>Croteau, Pascal</creatorcontrib><creatorcontrib>Higenell, Valerie</creatorcontrib><creatorcontrib>Izzi, Luisa</creatorcontrib><creatorcontrib>Spatz, Alan</creatorcontrib><creatorcontrib>Cohen, Victor</creatorcontrib><creatorcontrib>Batist, Gerald</creatorcontrib><creatorcontrib>Agulnik, Jason</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical proteomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Couëtoux du Tertre, Mathilde</au><au>Marques, Maud</au><au>McNamara, Suzan</au><au>Gambaro, Karen</au><au>Hoffert, Cyrla</au><au>Tremblay, Lise</au><au>Bouchard, Nicole</au><au>Diaconescu, Razvan</au><au>Blais, Normand</au><au>Couture, Christian</au><au>Pelsser, Vincent</au><au>Wang, Hangjun</au><au>McIntosh, Laura</au><au>Hindie, Valérie</au><au>Parent, Stephane</au><au>Cortes, Laetitia</au><au>Breton, Yannick-André</au><au>Pottiez, Gwenael</au><au>Croteau, Pascal</au><au>Higenell, Valerie</au><au>Izzi, Luisa</au><au>Spatz, Alan</au><au>Cohen, Victor</au><au>Batist, Gerald</au><au>Agulnik, Jason</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery of a putative blood-based protein signature associated with response to ALK tyrosine kinase inhibition</atitle><jtitle>Clinical proteomics</jtitle><addtitle>Clin Proteomics</addtitle><date>2020-02-07</date><risdate>2020</risdate><volume>17</volume><issue>1</issue><spage>5</spage><epage>5</epage><pages>5-5</pages><artnum>5</artnum><issn>1542-6416</issn><eissn>1559-0275</eissn><abstract>ALK tyrosine kinase inhibition has become a mainstay in the clinical management of ALK fusion positive NSCLC patients. Although ALK mutations can reliably predict the likelihood of response to ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, they cannot reliably predict response duration or intrinsic/extrinsic therapeutic resistance. To further refine the application of personalized medicine in this indication, this study aimed to identify prognostic proteomic biomarkers in ALK fusion positive NSCLC patients to crizotinib.
Twenty-four patients with advanced NSCLC harboring ALK fusion were administered crizotinib in a phase IV trial which included blood sampling prior to treatment. Targeted proteomics of 327 proteins using MRM-MS was used to measure plasma levels at baseline (including pre-treatment and early treatment blood samples) and assess potential clinical association.
Patients were categorized by duration of response: long-term responders [PFS ≥ 24 months (n = 7)], normal responders [3 < PFS < 24 months (n = 10)] and poor responders [PFS ≤ 3 months (n = 5)]. Several proteins were identified as differentially expressed between long-term responders and poor responders, including DPP4, KIT and LUM. Next, using machine learning algorithms, we evaluated the classification potential of 40 proteins. Finally, by integrating the different analytic methods, we selected 22 proteins as potential candidates for a blood-based prognostic signature of response to crizotinib in NSCLC patients harboring ALK fusion.
In conjunction with ALK mutation, the expression of this proteomic signature may represent a liquid biopsy-based marker of long-term response to crizotinib in NSCLC. Expanding the utility of prognostic biomarkers of response duration could influence choice of therapy, therapeutic sequencing, and potentially the need for alternative or combination therapy.
ClinicalTrials.gov, NCT02041468. Registered 22 January 2014, https://clinicaltrials.gov/ct2/show/NCT02041468?term=NCT02041468&rank=1.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>32055239</pmid><doi>10.1186/s12014-020-9269-6</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; SpringerLink Journals - AutoHoldings; PubMed Central Open Access; Springer Nature OA Free Journals |
| subjects | Algorithms Amino acids Biological markers Blood tests Clinical trials Crizotinib Data mining Health aspects Lung cancer Machine learning Non-small cell lung cancer Phenols (Class of compounds) Precision medicine Proteins Proteomics Tyrosine |
| title | Discovery of a putative blood-based protein signature associated with response to ALK tyrosine kinase inhibition |
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