Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders
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Abstract
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. See related commentary by Letai, p. 290. This article is highlighted in the In This Issue feature, p. 275
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High-throughput ex vivo drug screening is a powerful tool to identify effective compounds and drug repurposing candidates.
“High-throughput ex vivo drug screening is a powerful tool to identify effective compounds and drug repurposing candidates,10,11”
From Integrated drug profiling and CRISPR screening identify BCR::ABL1-independent vulnerabilities in chronic myeloid leukemia (2024) · cites this paper as [11]
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Self-citation
- Authors
- Kornauth, C., Pemovska, T., Vladimer, G. I., Bayer, G., Bergmann, M., Eder, S., Eichner, R., Erl, M., Esterbauer, H., Exner, R., Felsleitner-Hauer, V., Forte, M., Gaiger, A., Geissler, K., Greinix, H. T., Gstöttner, W., Hacker, M., Hartmann, B. L., Hauswirth, A. W., Heinemann, T., Heintel, D., Hoda, M. A., Hopfinger, G., Jaeger, U., Kazianka, L., Kenner, L., Kiesewetter, B., Krall, N., Krajnik, G., Kubicek, S., Le, T., Lubowitzki, S., Mayerhoefer, M. E., Menschel, E., Merkel, O., Miura, K., Müllauer, L., Neumeister, P., Noesslinger, T., Ocko, K., Öhler, L., Panny, M., Pichler, A., Porpaczy, E., Prager, G. W., Raderer, M., Ristl, R., Ruckser, R., Salamon, J., Schiefer, A.-I., Schmolke, A.-S., Schwarzinger, I., Selzer, E., Sillaber, C., Skrabs, C., Sperr, W. R., Srndic, I., Thalhammer, R., Valent, P., van der Kouwe, E., Vanura, K., Vogt, S., Waldstein, C., Wolf, D., Zielinski, C. C., Zojer, N., Simonitsch-Klupp, I., Superti-Furga, G., Snijder, B., & Staber, P. B.
- Affiliations
- Vienna General Hospital (AT)
- Austrian Academy of Sciences (AT)
- Medical University of Vienna (AT)
- Klinikum Klagenfurt (AT)
- 8Abteilung für Innere Medizin, Krankenhaus der Barmherzigen Brüder Salzburg, Salzburg, Austria.
- Universitätsklinikum Wiener Neustadt (AT)
- Sigmund Freud Privatuniversität Wien (AT)
- Medical University of Graz (AT)
- Landeskrankenhaus Feldkirch (AT)
- ETH Zurich (CH)
- 17Division of Medicine I, Klinik Ottakring, Vienna, Austria.
- 19Third Medical Department, Centre for Oncology and Haematology, Klinik Favoriten, Vienna, Austria.
- Universitätsklinikum St. Pölten (AT)
- Memorial Sloan Kettering Cancer Center (US)
- Hanusch Hospital (AT)
- Nihon University (JP)
- St. Josef-Krankenhaus Wien (AT)
- 29Second Medical Department, Klinik Donaustadt, Vienna, Austria.
- 30Department of Medicine, Landesklinikum Waidhofen a.d. Ybbs, Waidhofen-Ybbs, Austria.
- Ludwig Boltzmann Institute for Hematology and Oncology (AT)
- 1Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
- Innsbruck Medical University (AT)
- 5Department of Pathology, Medical University of Vienna, Vienna, Austria.
- 3CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
- Corresponding author
- Staber, Philipp B.
- ORCID
- Kornauth, Christoph
- Pemovska, Tea
- Vladimer, Gregory I.
- Bergmann, Michael
- Eichner, Ruth
- Esterbauer, Harald
- Exner, Ruth
- Gaiger, Alexander
- Geissler, Klaus
- Hacker, Marcus
- Hartmann, Bernd Lorenz
- Heinemann, Tim
- Hoda, Mir Alireza
- Hopfinger, Georg
- Kazianka, Lukas
- Kenner, Lukas
- Kiesewetter, Barbara
- Krall, Nikolaus
- Kubicek, Stefan
- Le, Trang
- Lubowitzki, Simone
- Mayerhoefer, Marius E.
- Merkel, Olaf
- Miura, Katsuhiro
- Müllauer, Leonhard
- Neumeister, Peter
- Panny, Michael
- Pichler, Alexander
- Porpaczy, Edit
- Prager, Gerald W.
- Ristl, Robin
- Schiefer, Ana-Iris
- Schwarzinger, Ilse
- Selzer, Edgar
- Sperr, Wolfgang R.
- Valent, Peter
- van der Kouwe, Emiel
- Vanura, Katrina
- Waldstein, Cora
- Wolf, Dominik
- Zielinski, Christoph C.
- Snijder, Berend
- Staber, Philipp B.
- Venue
- Cancer Discovery
- Published
- 2021-10-11
- Volume
- 12
- Issue
- 2
- Pages
- 372-387
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- PMC
- PMC9762339
- OpenAlex
- W3205761999
- Cited by
- 206
- References
- 43
- Citations by year
- 2026: 36 · 2025: 47 · 2024: 45 · 2023: 46 · 2022: 29 · 2021: 3
- FWCI
- 20.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cancer Discovery (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Vienna Science and Technology Fund (LS16-034)
- Austrian Science Fund (F4704-B20, F4711-B20, P27132-B20)
- European Molecular Biology Organization (1543-2012, 733-2016)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (PP00P3_163961, PP00P3_194809, CRSII5_193832)
- European Research Council
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Keywords
- functional precision medicine, hematologic malignancies, high-content imaging, drug response prediction, progression-free survival, exceptional responders
- MeSH terms
- Progression-Free Survival, Adult, Aged, Aged, 80 and over, Austria, Female, Humans, Male, Middle Aged, Cohort Studies, Hematologic Neoplasms, Young Adult, Precision Medicine, Molecular Targeted Therapy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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