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Zielgerichtete Therapieoptionen in der Uroonkologie

Precision oncology options in urological cancers

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Zusammenfassung

Fortschritte im molekulargenetischen Verständnis uroonkologischer Tumorerkrankungen ermöglichen die Identifikation zahlreicher neuer therapeutischer Zielstrukturen. Auf Grundlage routinemäßig anwendbarer Tumorsequenzierungen werden individuelle Therapieentscheidungen im Sinne der Präzisionsonkologie ermöglicht. In dieser Arbeit soll ein Überblick über die neuesten zielgerichteten Tumortherapien in der Behandlung des Prostata‑, Urothel- und Nierenzellkarzinoms gegeben werden. Es werden aktuelle Studien zur Anwendung von FGFR-Inhibitoren („fibroblast growth factor receptor“) im metastasierten Urothelkarzinom diskutiert, welche ein hohes Tumoransprechen bei Patienten mit FGFR-Mutationen zeigen. PARP-Inhibitoren („Poly-[ADP-Ribose-]Polymerase“) finden Anwendung in der Therapie des metastasierten Prostatakarzinoms, insbesondere Patienten mit einer BRCA-Mutation („BReast CAncer gene“) weisen hohe radiologische Ansprechraten auf, wobei auch zuletzt veröffentlichte Ergebnisse zu Kombinationstherapien von PARP-Inhibitoren mit einer der neuen antihormonellen Substanz diskutiert werden. Darüber hinaus werden Studien im Stadium des metastasierten Prostatakarzinoms, in denen Medikamente, welche die PI3K (Phosphatidylinositol-3-Kinase)/AKT/mTOR („mammalian target of rapamycine“)- und VEGF-Signalwegskaskaden („vascular endothelial growth factor“) verändern, zusammengefasst und deren therapeutische Potenziale dargestellt. Beim metastasierten Nierenzellkarzinom bietet ein HIF-2a-Inhibitor („hypoxia inducible factor“) eine vielversprechende neue therapeutische Option. Die molekulare Diagnostik zur Therapiefindung für Patientensubgruppen zum richtigen Zeitpunkt nimmt einen immer wichtigeren Stellenwert in der uroonkologischen Präzisionsmedizin ein.

Abstract

Advancements in the molecular genetic understanding of urological tumors have enabled the identification of numerous new therapeutic targets. Based on routinely applicable tumor sequencing, individual treatment decisions have been introduced in the context of precision oncology. This work provides an overview of the latest targeted tumor therapies in the treatment of prostate cancer, urothelial carcinoma, and renal cell carcinoma. Current studies on the administration of FGFR-inhibitors (“fibroblast growth factor receptor”) in metastatic urothelial carcinoma show a high tumor response in patients with selected FGFR alterations. PARP-inhibitors (“Poly-[ADP-Ribose-]Polymerase”) are routinely used in the treatment of metastatic prostate cancer. Patients with a BRCA mutation (“BReast CAncer gene”) show high radiological response rates. Moreover, we discuss the latest results of the combination of PARP inhibitors with novel androgen receptor pathway inhibitors. In metastatic prostate cancer, there are numerous ongoing studies evaluating the promising drug targets PI3K/AKT/mTOR (“Phosphatidylinositol-3-Kinase”)/AKT/mTOR (“mammalian target of rapamycine”) and VEGF signaling pathways (“vascular endothelial growth factor”). A HIF-2a inhibitor (“hypoxia inducible factor”) offers a promising new therapeutic option for metastatic renal cell carcinoma. Overall, molecular diagnostics to determine the right therapy for the right patient subgroup at the right time is important for uro-oncological precision medicine.

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Authors and Affiliations

  1. Klinik für Urologie, Charité – Universitätsmedizin Berlin, Charité Platz 1, 10117, Berlin, Deutschland

    Antonia Franz, Henning Plage, Annika Fendler, Thorsten Schlomm &  Kira Kornienko

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Correspondence to Kira Kornienko.

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A. Franz, H. Plage, A. Fendler, T. Schlomm und K. Kornienko geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Franz, A., Plage, H., Fendler, A. et al. Zielgerichtete Therapieoptionen in der Uroonkologie. Urologie 62, 696–704 (2023). https://doi.org/10.1007/s00120-023-02119-z

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