Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders
Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may...
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| Veröffentlicht in: | Cancer discovery 2022-02, Vol.12 (2), p.372-387 |
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| creator | Kornauth, Christoph Pemovska, Tea Vladimer, Gregory I Bayer, Günther Bergmann, Michael Eder, Sandra Eichner, Ruth Erl, Martin Esterbauer, Harald Exner, Ruth Felsleitner-Hauer, Verena Forte, Maurizio Gaiger, Alexander Geissler, Klaus Greinix, Hildegard T Gstöttner, Wolfgang Hacker, Marcus Hartmann, Bernd Lorenz Hauswirth, Alexander W Heinemann, Tim Heintel, Daniel Hoda, Mir Alireza Hopfinger, Georg Jaeger, Ulrich Kazianka, Lukas Kenner, Lukas Kiesewetter, Barbara Krall, Nikolaus Krajnik, Gerhard Kubicek, Stefan Le, Trang Lubowitzki, Simone Mayerhoefer, Marius E Menschel, Elisabeth Merkel, Olaf Miura, Katsuhiro Müllauer, Leonhard Neumeister, Peter Noesslinger, Thomas Ocko, Katharina Öhler, Leopold Panny, Michael Pichler, Alexander Porpaczy, Edit Prager, Gerald W Raderer, Markus Ristl, Robin Ruckser, Reinhard Salamon, Julius Schiefer, Ana-Iris Schmolke, Ann-Sofie Schwarzinger, Ilse Selzer, Edgar Sillaber, Christian Skrabs, Cathrin Sperr, Wolfgang R Srndic, Ismet Thalhammer, Renate Valent, Peter van der Kouwe, Emiel Vanura, Katrina Vogt, Stefan Waldstein, Cora Wolf, Dominik Zielinski, Christoph C Zojer, Niklas Simonitsch-Klupp, Ingrid Superti-Furga, Giulio Snijder, Berend Staber, Philipp B |
| description | Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers. SIGNIFICANCE: This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer.
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| doi_str_mv | 10.1158/2159-8290.CD-21-0538 |
| format | Article |
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However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers. SIGNIFICANCE: This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer.
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.</description><identifier>ISSN: 2159-8274</identifier><identifier>EISSN: 2159-8290</identifier><identifier>DOI: 10.1158/2159-8290.CD-21-0538</identifier><identifier>PMID: 34635570</identifier><language>eng</language><publisher>United States: American Association for Cancer Research</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Austria ; Cohort Studies ; Female ; Hematologic Neoplasms - drug therapy ; Hematologic Neoplasms - mortality ; Humans ; Male ; Middle Aged ; Molecular Targeted Therapy ; Precision Medicine ; Progression-Free Survival ; Young Adult</subject><ispartof>Cancer discovery, 2022-02, Vol.12 (2), p.372-387</ispartof><rights>2021 The Authors; Published by the American Association for Cancer Research.</rights><rights>2021 The Authors; Published by the American Association for Cancer Research 2021 American Association for Cancer Research</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-75411f43fc764d9074ff1ab29834eacd5f90c4695547089b5a211d49da02be8c3</citedby><cites>FETCH-LOGICAL-c459t-75411f43fc764d9074ff1ab29834eacd5f90c4695547089b5a211d49da02be8c3</cites><orcidid>0000-0001-7072-5152 ; 0000-0003-4205-7585 ; 0000-0002-2217-4998 ; 0000-0001-8808-1850 ; 0000-0002-3399-078X ; 0000-0003-3386-6583 ; 0000-0002-4618-789X ; 0000-0002-2761-5334 ; 0000-0003-0855-8343 ; 0000-0003-2184-1338 ; 0000-0002-5490-2371 ; 0000-0001-8529-1166 ; 0000-0003-2951-4905 ; 0000-0001-8831-3746</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3343,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34635570$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kornauth, Christoph</creatorcontrib><creatorcontrib>Pemovska, Tea</creatorcontrib><creatorcontrib>Vladimer, Gregory I</creatorcontrib><creatorcontrib>Bayer, Günther</creatorcontrib><creatorcontrib>Bergmann, Michael</creatorcontrib><creatorcontrib>Eder, Sandra</creatorcontrib><creatorcontrib>Eichner, Ruth</creatorcontrib><creatorcontrib>Erl, Martin</creatorcontrib><creatorcontrib>Esterbauer, Harald</creatorcontrib><creatorcontrib>Exner, Ruth</creatorcontrib><creatorcontrib>Felsleitner-Hauer, Verena</creatorcontrib><creatorcontrib>Forte, Maurizio</creatorcontrib><creatorcontrib>Gaiger, Alexander</creatorcontrib><creatorcontrib>Geissler, Klaus</creatorcontrib><creatorcontrib>Greinix, Hildegard T</creatorcontrib><creatorcontrib>Gstöttner, Wolfgang</creatorcontrib><creatorcontrib>Hacker, Marcus</creatorcontrib><creatorcontrib>Hartmann, Bernd Lorenz</creatorcontrib><creatorcontrib>Hauswirth, Alexander W</creatorcontrib><creatorcontrib>Heinemann, Tim</creatorcontrib><creatorcontrib>Heintel, Daniel</creatorcontrib><creatorcontrib>Hoda, Mir Alireza</creatorcontrib><creatorcontrib>Hopfinger, Georg</creatorcontrib><creatorcontrib>Jaeger, Ulrich</creatorcontrib><creatorcontrib>Kazianka, Lukas</creatorcontrib><creatorcontrib>Kenner, Lukas</creatorcontrib><creatorcontrib>Kiesewetter, Barbara</creatorcontrib><creatorcontrib>Krall, Nikolaus</creatorcontrib><creatorcontrib>Krajnik, Gerhard</creatorcontrib><creatorcontrib>Kubicek, Stefan</creatorcontrib><creatorcontrib>Le, Trang</creatorcontrib><creatorcontrib>Lubowitzki, Simone</creatorcontrib><creatorcontrib>Mayerhoefer, Marius E</creatorcontrib><creatorcontrib>Menschel, Elisabeth</creatorcontrib><creatorcontrib>Merkel, Olaf</creatorcontrib><creatorcontrib>Miura, Katsuhiro</creatorcontrib><creatorcontrib>Müllauer, Leonhard</creatorcontrib><creatorcontrib>Neumeister, Peter</creatorcontrib><creatorcontrib>Noesslinger, Thomas</creatorcontrib><creatorcontrib>Ocko, Katharina</creatorcontrib><creatorcontrib>Öhler, Leopold</creatorcontrib><creatorcontrib>Panny, Michael</creatorcontrib><creatorcontrib>Pichler, Alexander</creatorcontrib><creatorcontrib>Porpaczy, Edit</creatorcontrib><creatorcontrib>Prager, Gerald W</creatorcontrib><creatorcontrib>Raderer, Markus</creatorcontrib><creatorcontrib>Ristl, Robin</creatorcontrib><creatorcontrib>Ruckser, Reinhard</creatorcontrib><creatorcontrib>Salamon, Julius</creatorcontrib><creatorcontrib>Schiefer, Ana-Iris</creatorcontrib><creatorcontrib>Schmolke, Ann-Sofie</creatorcontrib><creatorcontrib>Schwarzinger, Ilse</creatorcontrib><creatorcontrib>Selzer, Edgar</creatorcontrib><creatorcontrib>Sillaber, Christian</creatorcontrib><creatorcontrib>Skrabs, Cathrin</creatorcontrib><creatorcontrib>Sperr, Wolfgang R</creatorcontrib><creatorcontrib>Srndic, Ismet</creatorcontrib><creatorcontrib>Thalhammer, Renate</creatorcontrib><creatorcontrib>Valent, Peter</creatorcontrib><creatorcontrib>van der Kouwe, Emiel</creatorcontrib><creatorcontrib>Vanura, Katrina</creatorcontrib><creatorcontrib>Vogt, Stefan</creatorcontrib><creatorcontrib>Waldstein, Cora</creatorcontrib><creatorcontrib>Wolf, Dominik</creatorcontrib><creatorcontrib>Zielinski, Christoph C</creatorcontrib><creatorcontrib>Zojer, Niklas</creatorcontrib><creatorcontrib>Simonitsch-Klupp, Ingrid</creatorcontrib><creatorcontrib>Superti-Furga, Giulio</creatorcontrib><creatorcontrib>Snijder, Berend</creatorcontrib><creatorcontrib>Staber, Philipp B</creatorcontrib><title>Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders</title><title>Cancer discovery</title><addtitle>Cancer Discov</addtitle><description>Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers. SIGNIFICANCE: This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer.
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.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Austria</subject><subject>Cohort Studies</subject><subject>Female</subject><subject>Hematologic Neoplasms - drug therapy</subject><subject>Hematologic Neoplasms - mortality</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Molecular Targeted Therapy</subject><subject>Precision Medicine</subject><subject>Progression-Free Survival</subject><subject>Young 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Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders</title><author>Kornauth, Christoph ; Pemovska, Tea ; Vladimer, Gregory I ; Bayer, Günther ; Bergmann, Michael ; Eder, Sandra ; Eichner, Ruth ; Erl, Martin ; Esterbauer, Harald ; Exner, Ruth ; Felsleitner-Hauer, Verena ; Forte, Maurizio ; Gaiger, Alexander ; Geissler, Klaus ; Greinix, Hildegard T ; Gstöttner, Wolfgang ; Hacker, Marcus ; Hartmann, Bernd Lorenz ; Hauswirth, Alexander W ; Heinemann, Tim ; Heintel, Daniel ; Hoda, Mir Alireza ; Hopfinger, Georg ; Jaeger, Ulrich ; Kazianka, Lukas ; Kenner, Lukas ; Kiesewetter, Barbara ; Krall, Nikolaus ; Krajnik, Gerhard ; Kubicek, Stefan ; Le, Trang ; Lubowitzki, Simone ; Mayerhoefer, Marius E ; Menschel, Elisabeth ; Merkel, Olaf ; Miura, Katsuhiro ; Müllauer, Leonhard ; Neumeister, Peter ; Noesslinger, Thomas ; Ocko, Katharina ; Öhler, Leopold ; Panny, Michael ; Pichler, Alexander ; Porpaczy, Edit ; Prager, Gerald W ; Raderer, Markus ; Ristl, Robin ; Ruckser, Reinhard ; Salamon, Julius ; Schiefer, Ana-Iris ; Schmolke, Ann-Sofie ; Schwarzinger, Ilse ; Selzer, Edgar ; Sillaber, Christian ; Skrabs, Cathrin ; Sperr, Wolfgang R ; Srndic, Ismet ; Thalhammer, Renate ; Valent, Peter ; van der Kouwe, Emiel ; Vanura, Katrina ; Vogt, Stefan ; Waldstein, Cora ; Wolf, Dominik ; Zielinski, Christoph C ; Zojer, Niklas ; Simonitsch-Klupp, Ingrid ; Superti-Furga, Giulio ; Snijder, Berend ; Staber, Philipp B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-75411f43fc764d9074ff1ab29834eacd5f90c4695547089b5a211d49da02be8c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Austria</topic><topic>Cohort Studies</topic><topic>Female</topic><topic>Hematologic Neoplasms - drug therapy</topic><topic>Hematologic Neoplasms - mortality</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Molecular Targeted Therapy</topic><topic>Precision Medicine</topic><topic>Progression-Free Survival</topic><topic>Young Adult</topic><toplevel>online_resources</toplevel><creatorcontrib>Kornauth, Christoph</creatorcontrib><creatorcontrib>Pemovska, Tea</creatorcontrib><creatorcontrib>Vladimer, Gregory I</creatorcontrib><creatorcontrib>Bayer, Günther</creatorcontrib><creatorcontrib>Bergmann, Michael</creatorcontrib><creatorcontrib>Eder, Sandra</creatorcontrib><creatorcontrib>Eichner, Ruth</creatorcontrib><creatorcontrib>Erl, Martin</creatorcontrib><creatorcontrib>Esterbauer, Harald</creatorcontrib><creatorcontrib>Exner, Ruth</creatorcontrib><creatorcontrib>Felsleitner-Hauer, Verena</creatorcontrib><creatorcontrib>Forte, Maurizio</creatorcontrib><creatorcontrib>Gaiger, Alexander</creatorcontrib><creatorcontrib>Geissler, Klaus</creatorcontrib><creatorcontrib>Greinix, Hildegard T</creatorcontrib><creatorcontrib>Gstöttner, Wolfgang</creatorcontrib><creatorcontrib>Hacker, Marcus</creatorcontrib><creatorcontrib>Hartmann, Bernd Lorenz</creatorcontrib><creatorcontrib>Hauswirth, Alexander W</creatorcontrib><creatorcontrib>Heinemann, Tim</creatorcontrib><creatorcontrib>Heintel, Daniel</creatorcontrib><creatorcontrib>Hoda, Mir Alireza</creatorcontrib><creatorcontrib>Hopfinger, Georg</creatorcontrib><creatorcontrib>Jaeger, Ulrich</creatorcontrib><creatorcontrib>Kazianka, Lukas</creatorcontrib><creatorcontrib>Kenner, Lukas</creatorcontrib><creatorcontrib>Kiesewetter, Barbara</creatorcontrib><creatorcontrib>Krall, Nikolaus</creatorcontrib><creatorcontrib>Krajnik, Gerhard</creatorcontrib><creatorcontrib>Kubicek, Stefan</creatorcontrib><creatorcontrib>Le, Trang</creatorcontrib><creatorcontrib>Lubowitzki, Simone</creatorcontrib><creatorcontrib>Mayerhoefer, Marius E</creatorcontrib><creatorcontrib>Menschel, Elisabeth</creatorcontrib><creatorcontrib>Merkel, Olaf</creatorcontrib><creatorcontrib>Miura, Katsuhiro</creatorcontrib><creatorcontrib>Müllauer, Leonhard</creatorcontrib><creatorcontrib>Neumeister, Peter</creatorcontrib><creatorcontrib>Noesslinger, Thomas</creatorcontrib><creatorcontrib>Ocko, Katharina</creatorcontrib><creatorcontrib>Öhler, Leopold</creatorcontrib><creatorcontrib>Panny, Michael</creatorcontrib><creatorcontrib>Pichler, Alexander</creatorcontrib><creatorcontrib>Porpaczy, Edit</creatorcontrib><creatorcontrib>Prager, Gerald W</creatorcontrib><creatorcontrib>Raderer, Markus</creatorcontrib><creatorcontrib>Ristl, Robin</creatorcontrib><creatorcontrib>Ruckser, Reinhard</creatorcontrib><creatorcontrib>Salamon, Julius</creatorcontrib><creatorcontrib>Schiefer, Ana-Iris</creatorcontrib><creatorcontrib>Schmolke, Ann-Sofie</creatorcontrib><creatorcontrib>Schwarzinger, Ilse</creatorcontrib><creatorcontrib>Selzer, Edgar</creatorcontrib><creatorcontrib>Sillaber, Christian</creatorcontrib><creatorcontrib>Skrabs, Cathrin</creatorcontrib><creatorcontrib>Sperr, Wolfgang R</creatorcontrib><creatorcontrib>Srndic, Ismet</creatorcontrib><creatorcontrib>Thalhammer, Renate</creatorcontrib><creatorcontrib>Valent, Peter</creatorcontrib><creatorcontrib>van der Kouwe, Emiel</creatorcontrib><creatorcontrib>Vanura, Katrina</creatorcontrib><creatorcontrib>Vogt, Stefan</creatorcontrib><creatorcontrib>Waldstein, Cora</creatorcontrib><creatorcontrib>Wolf, Dominik</creatorcontrib><creatorcontrib>Zielinski, Christoph C</creatorcontrib><creatorcontrib>Zojer, Niklas</creatorcontrib><creatorcontrib>Simonitsch-Klupp, Ingrid</creatorcontrib><creatorcontrib>Superti-Furga, Giulio</creatorcontrib><creatorcontrib>Snijder, Berend</creatorcontrib><creatorcontrib>Staber, Philipp B</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer discovery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kornauth, Christoph</au><au>Pemovska, Tea</au><au>Vladimer, Gregory I</au><au>Bayer, Günther</au><au>Bergmann, Michael</au><au>Eder, Sandra</au><au>Eichner, Ruth</au><au>Erl, Martin</au><au>Esterbauer, Harald</au><au>Exner, Ruth</au><au>Felsleitner-Hauer, Verena</au><au>Forte, Maurizio</au><au>Gaiger, Alexander</au><au>Geissler, Klaus</au><au>Greinix, Hildegard T</au><au>Gstöttner, Wolfgang</au><au>Hacker, Marcus</au><au>Hartmann, Bernd Lorenz</au><au>Hauswirth, Alexander W</au><au>Heinemann, Tim</au><au>Heintel, Daniel</au><au>Hoda, Mir Alireza</au><au>Hopfinger, Georg</au><au>Jaeger, Ulrich</au><au>Kazianka, Lukas</au><au>Kenner, Lukas</au><au>Kiesewetter, Barbara</au><au>Krall, Nikolaus</au><au>Krajnik, Gerhard</au><au>Kubicek, Stefan</au><au>Le, Trang</au><au>Lubowitzki, Simone</au><au>Mayerhoefer, Marius E</au><au>Menschel, Elisabeth</au><au>Merkel, Olaf</au><au>Miura, Katsuhiro</au><au>Müllauer, Leonhard</au><au>Neumeister, Peter</au><au>Noesslinger, Thomas</au><au>Ocko, Katharina</au><au>Öhler, Leopold</au><au>Panny, Michael</au><au>Pichler, Alexander</au><au>Porpaczy, Edit</au><au>Prager, Gerald W</au><au>Raderer, Markus</au><au>Ristl, Robin</au><au>Ruckser, Reinhard</au><au>Salamon, Julius</au><au>Schiefer, Ana-Iris</au><au>Schmolke, Ann-Sofie</au><au>Schwarzinger, Ilse</au><au>Selzer, Edgar</au><au>Sillaber, Christian</au><au>Skrabs, Cathrin</au><au>Sperr, Wolfgang R</au><au>Srndic, Ismet</au><au>Thalhammer, Renate</au><au>Valent, Peter</au><au>van der Kouwe, Emiel</au><au>Vanura, Katrina</au><au>Vogt, Stefan</au><au>Waldstein, Cora</au><au>Wolf, Dominik</au><au>Zielinski, Christoph C</au><au>Zojer, Niklas</au><au>Simonitsch-Klupp, Ingrid</au><au>Superti-Furga, Giulio</au><au>Snijder, Berend</au><au>Staber, Philipp B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders</atitle><jtitle>Cancer discovery</jtitle><addtitle>Cancer Discov</addtitle><date>2022-02-01</date><risdate>2022</risdate><volume>12</volume><issue>2</issue><spage>372</spage><epage>387</epage><pages>372-387</pages><issn>2159-8274</issn><eissn>2159-8290</eissn><abstract>Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers. SIGNIFICANCE: This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer.
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.</abstract><cop>United States</cop><pub>American Association for Cancer Research</pub><pmid>34635570</pmid><doi>10.1158/2159-8290.CD-21-0538</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0001-7072-5152</orcidid><orcidid>https://orcid.org/0000-0003-4205-7585</orcidid><orcidid>https://orcid.org/0000-0002-2217-4998</orcidid><orcidid>https://orcid.org/0000-0001-8808-1850</orcidid><orcidid>https://orcid.org/0000-0002-3399-078X</orcidid><orcidid>https://orcid.org/0000-0003-3386-6583</orcidid><orcidid>https://orcid.org/0000-0002-4618-789X</orcidid><orcidid>https://orcid.org/0000-0002-2761-5334</orcidid><orcidid>https://orcid.org/0000-0003-0855-8343</orcidid><orcidid>https://orcid.org/0000-0003-2184-1338</orcidid><orcidid>https://orcid.org/0000-0002-5490-2371</orcidid><orcidid>https://orcid.org/0000-0001-8529-1166</orcidid><orcidid>https://orcid.org/0000-0003-2951-4905</orcidid><orcidid>https://orcid.org/0000-0001-8831-3746</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2159-8274 |
| ispartof | Cancer discovery, 2022-02, Vol.12 (2), p.372-387 |
| issn | 2159-8274 2159-8290 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9762339 |
| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Adult Aged Aged, 80 and over Austria Cohort Studies Female Hematologic Neoplasms - drug therapy Hematologic Neoplasms - mortality Humans Male Middle Aged Molecular Targeted Therapy Precision Medicine Progression-Free Survival Young Adult |
| title | Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-18T22%3A42%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Functional%20Precision%20Medicine%20Provides%20Clinical%20Benefit%20in%20Advanced%20Aggressive%20Hematologic%20Cancers%20and%20Identifies%20Exceptional%20Responders&rft.jtitle=Cancer%20discovery&rft.au=Kornauth,%20Christoph&rft.date=2022-02-01&rft.volume=12&rft.issue=2&rft.spage=372&rft.epage=387&rft.pages=372-387&rft.issn=2159-8274&rft.eissn=2159-8290&rft_id=info:doi/10.1158/2159-8290.CD-21-0538&rft_dat=%3Cproquest_pubme%3E2581290206%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2581290206&rft_id=info:pmid/34635570&rfr_iscdi=true |