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Präzisionsmedizin in der Onkologie

Precision medicine in oncology

  • Schwerpunkt: Präzisionsmedizin
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Zusammenfassung

Die Personalisierung der onkologischen Therapie basiert heute überwiegend auf der Tumorbiologie, die in genomische Biomarker übersetzt wird. Mutationen in Onkogenen und Tumorsuppressorgenen bilden Angriffspunkte für zielgerichtete Wirkstoffe und werden umgekehrt genutzt, um maßgeschneiderte Behandlungsempfehlungen abzuleiten. Immer kostengünstigere und schnellere Verfahren zur DNA-Sequenzierung machen diese genomisch informierte Medizin grundsätzlich routinefähig. Die Verknüpfung genomischen, biologischen und klinischen Wissens übernehmen sogenannte molekulare Tumorboards, die in den letzten Jahren an vielen onkologischen Zentren in Deutschland und weltweit etabliert wurden. Im vorliegenden Beitrag werden die Chancen und Limitationen dieser Umsetzung der Präzisionsonkologie aufgezeigt und zukünftige Entwicklungsmöglichkeiten sowie alternative Strategien zur Individualisierung onkologischer Therapien schlaglichtartig beleuchtet.

Abstract

Personalized oncology according to current practice is primarily based on tumor biology, which is translated into genomic biomarkers. Mutations in oncogenes and tumor suppressor genes are targeted by rationally designed drugs and, conversely, are used to inform tailored treatment strategies. Faster and cheaper technologies for DNA sequencing enable genomic medicine in a clinical routine setting. Genomic features, tumor biology and clinical implications are integrated into individual therapy recommendations by molecular tumor boards, which have been established at many cancer centers in Germany and worldwide throughout recent years. This article discusses the promises and limitations of genomics-centered precision oncology and highlights future avenues and alternative approaches to individualize cancer treatment.

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Literatur

  1. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  CAS  PubMed  Google Scholar 

  2. OncoKB—MSK’s Precision Oncology Knowledge Base.

  3. Hoefflin R, Lazarou A, Hess ME et al (2021) Transitioning the molecular tumor board from proof of concept to clinical routine: a German single-center analysis. Cancers 13:1151. https://doi.org/10.3390/cancers13051151

    Article  PubMed  PubMed Central  Google Scholar 

  4. Massard C, Michiels S, Ferté C et al (2017) High-throughput genomics and clinical outcome in hard-to-treat advanced cancers: results of the MOSCATO 01 trial. Cancer Discov 7(6):586. https://doi.org/10.1158/2159-8290.CD-16-1396

    Article  CAS  PubMed  Google Scholar 

  5. Scheiter A, Hierl F, Lüke F et al (2023) Critical evaluation of molecular tumour board outcomes following 2 years of clinical practice in a Comprehensive Cancer Centre. Br J Cancer 128:1134–1147. https://doi.org/10.1038/s41416-022-02120-x

    Article  CAS  PubMed  Google Scholar 

  6. Tarawneh TS, Rodepeter FR, Teply-Szymanski J et al (2022) Combined focused next-generation sequencing assays to guide precision oncology in solid tumors: a retrospective analysis from an institutional molecular tumor board. Cancers. https://doi.org/10.3390/cancers14184430

    Article  PubMed  PubMed Central  Google Scholar 

  7. Horak P, Heining C, Kreutzfeldt S et al (2021) Comprehensive genomic and transcriptomic analysis for guiding therapeutic decisions in patients with rare cancers. Cancer Discov 11:2780–2795. https://doi.org/10.1158/2159-8290.CD-21-0126

    Article  CAS  PubMed  Google Scholar 

  8. Illert AL, Stenzinger A, Bitzer M et al (2023) The German network for personalized medicine to enhance patient care and translational research. Nat Med. https://doi.org/10.1038/s41591-023-02354-z

    Article  PubMed  Google Scholar 

  9. Bruford EA, Antonescu CR, Carroll AJ, Chinnaiyan A, Cree IA, Cross NCP, Dalgleish R, Gale RP, Harrison CJ, Hastings RJ, Huret JL, Johansson B, Le Beau M, Mecucci C, Mertens F, Verhaak R, Mitelman F (2021) HUGO Gene Nomenclature Committee (HGNC) recommendations for the designation of gene fusions. Leukemia 35(11):3040–3043. https://doi.org/10.1038/s41375-021-01436-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hochhaus A, Baccarani M, Silver RT et al (2020) European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia 34:966–984. https://doi.org/10.1038/s41375-020-0776-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cobain EF, Wu Y‑M, Vats P et al (2021) Assessment of clinical benefit of integrative genomic profiling in advanced solid tumors. JAMA Oncol 7:525–533. https://doi.org/10.1001/jamaoncol.2020.7987

    Article  PubMed  Google Scholar 

  12. Crimini E, Repetto M, Tarantino P et al (2022) Challenges and obstacles in applying therapeutical indications formulated in molecular tumor boards. Cancers. https://doi.org/10.3390/cancers14133193

    Article  PubMed  PubMed Central  Google Scholar 

  13. Le Tourneau C, Delord JP, Gonçalves A et al (2015) Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol 16:1324–1334. https://doi.org/10.1016/S1470-2045(15)00188-6

    Article  CAS  PubMed  Google Scholar 

  14. O’Dwyer PJ, Gray RJ, Flaherty KT et al (2023) The NCI-MATCH trial: lessons for precision oncology. Nat Med 29:1349–1357. https://doi.org/10.1038/s41591-023-02379-4

    Article  CAS  PubMed  Google Scholar 

  15. Hill W, Lim EL, Weeden CE et al (2023) Lung adenocarcinoma promotion by air pollutants. Nature 616:159–167. https://doi.org/10.1038/s41586-023-05874-3

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  16. McGranahan N, Swanton C (2017) Clonal heterogeneity and tumor evolution: past, present, and the future. Cell 168:613–628. https://doi.org/10.1016/j.cell.2017.01.018

    Article  CAS  PubMed  Google Scholar 

  17. Ogitani Y, Hagihara K, Oitate M et al (2016) Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody–drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity. Cancer Sci 107:1039–1046. https://doi.org/10.1111/cas.12966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Andre F, Filleron T, Kamal M et al (2022) Genomics to select treatment for patients with metastatic breast cancer. Nature 610:343–348. https://doi.org/10.1038/s41586-022-05068-3

    Article  ADS  CAS  PubMed  Google Scholar 

  19. Mateo J, Chakravarty D, Dienstmann R et al (2018) A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Ann Oncol 29:1895–1902. https://doi.org/10.1093/annonc/mdy263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Christofyllakis K, Bittenbring JT, Thurner L et al (2022) Cost-effectiveness of precision cancer medicine-current challenges in the use of next generation sequencing for comprehensive tumour genomic profiling and the role of clinical utility frameworks (Review). Mol Clin Oncol 16:21. https://doi.org/10.3892/mco.2021.2453

    Article  PubMed  Google Scholar 

  21. Wahida A, Buschhorn L, Fröhling S et al (2023) The coming decade in precision oncology: six riddles. Nat Rev Cancer 23:43–54. https://doi.org/10.1038/s41568-022-00529-3

    Article  CAS  PubMed  Google Scholar 

  22. Cercek A, Lumish M, Sinopoli J et al (2022) PD‑1 blockade in mismatch repair–deficient, locally advanced rectal cancer. N Engl J Med 386:2363–2376. https://doi.org/10.1056/NEJMoa2201445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kato S, Kim KH, Lim HJ et al (2020) Real-world data from a molecular tumor board demonstrates improved outcomes with a precision N‑of-One strategy. Nat Commun 11:4965. https://doi.org/10.1038/s41467-020-18613-3

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  24. Sicklick JK, Kato S, Okamura R et al (2021) Molecular profiling of advanced malignancies guides first-line N‑of‑1 treatments in the I‑PREDICT treatment-naïve study. Genome Med 13:155. https://doi.org/10.1186/s13073-021-00969-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hoadley KA, Yau C, Hinoue T et al (2018) Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer. Cell 173:291–304.e6. https://doi.org/10.1016/j.cell.2018.03.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Letai A, Bhola P, Welm AL (2022) Functional precision oncology: Testing tumors with drugs to identify vulnerabilities and novel combinations. Cancer Cell 40:26–35. https://doi.org/10.1016/j.ccell.2021.12.004

    Article  CAS  PubMed  Google Scholar 

  27. Bose S, Clevers H, Shen X (2021) Promises and challenges of organoid-guided precision medicine. Med 2:1011–1026. https://doi.org/10.1016/j.medj.2021.08.005

    Article  PubMed  Google Scholar 

  28. Irvine DJ, Maus MV, Mooney DJ, Wong WW (2022) The future of engineered immune cell therapies. Science 378(80):853–858. https://doi.org/10.1126/science.abq6990

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lang F, Schrörs B, Löwer M et al (2022) Identification of neoantigens for individualized therapeutic cancer vaccines. Nat Rev Drug Discov 21:261–282. https://doi.org/10.1038/s41573-021-00387-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Coleman N, Rodon J (2021) Taking aim at the undruggable. Am Soc Clin Oncol Educ B. https://doi.org/10.1200/EDBK_325885

    Article  Google Scholar 

  31. Singh V, Khan N, Jayandharan GR (2022) Vector engineering, strategies and targets in cancer gene therapy. Cancer Gene Ther 29:402–417. https://doi.org/10.1038/s41417-021-00331-7

    Article  CAS  PubMed  Google Scholar 

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Danksagung

Die Autorin dankt Prof. Lena Illert und PD Dr. Cornelia Brendel für die kritische Durchsicht des Manuskripts.

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Authors and Affiliations

  1. Klinik für Hämatologie, Onkologie und Immunologie, Universitätsklinikum Gießen und Marburg GmbH, Standort Marburg, Philipps-Universität Marburg, Baldingerstr., 35043, Marburg, Deutschland

    Elisabeth Mack

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Correspondence to Elisabeth Mack.

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Interessenkonflikt

E. Mack ist als Referentin für die Firmen Roche und Boehringer Ingelheim tätig und erhielt ein Beraterhonorar von Roche.

Für diesen Beitrag wurden von der Autorin keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Andreas Neubauer, Marburg

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Mack, E. Präzisionsmedizin in der Onkologie. Innere Medizin 65, 194–201 (2024). https://doi.org/10.1007/s00108-023-01614-x

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