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Molekulare zielgerichtete Therapie und Immuntherapie des Prostatakarzinoms

Targeted molecular therapy and immunotherapy for prostate cancer

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Zusammenfassung

Über Jahrzehnte basierte die Behandlung des fortgeschrittenen Prostatakarzinoms vorwiegend auf der Manipulation des Androgenrezeptor-gesteuerten Proliferationswegs. Chemotherapien spielten erst mit dem Aufkommen der Taxane eine zusätzliche wichtige Rolle. Der Fortschritt in der translationalen Forschung der letzten Jahre brachte Bewegung und einschlägige Innovationen in das therapeutische Umfeld. Zielgerichtete Therapien rückten mit der Entschlüsselung der HRD-Maschinerie („homologous repair deficiency“) und deren medikamentöser Beeinflussbarkeit durch PARP-Inhibitoren (Poly-Adenyl-Ribose-Polymerase) in den Therapiefokus für ausgewählte Patienten. Die erste positive Phase-III-Studie für PARP-Inhibitoren liegt bereits vor. Darüber hinaus macht auch die in der Onkologie mittlerweile weitverbreitete Immuntherapie beim Prostatakarzinom Fortschritte, sowohl Checkpoint-Inhibitoren als auch bispezifische Antikörper konnten klinisch sinnvolle Aktivitäten zeigen. Noch früh in der Entwicklung befinden sich zelluläre Therapien wie CAR(„chimeric antigen receptor“)-T-Zellen, die gegen PSMA (prostataspezifisches Membranantigen) gerichtet sind. In diesem Review möchten die Autoren eine zusammenfassende Übersicht über Grundlagen und klinische Entwicklung dieser neuen Therapien geben.

Abstract

For decades, the treatment of advanced prostate cancer was mainly based on the manipulation of the androgen receptor-controlled proliferation pathway. Chemotherapy only played an additional important role with the advent of taxanes. The progress in translational research in recent years has led to innovations in the therapeutic environment. With the decoding of the homologous repair deficiency (HRD) machinery and its ability to be influenced by PARP inhibitors, targeted therapies moved into the therapeutic focus for selected patients. The first positive phase III study for PARP inhibitors is already available. In addition, immunotherapy for the treatment of prostate cancer, which is now widely used in oncology, is also making progress; both checkpoint inhibitors and bispecific antibodies have shown clinically useful activities. Cellular therapies such as CAR T cells, which are directed against prostate-specific membrane antigen (PSMA), are still at an early stage of development. In this review, the authors provide a summary of the basic principles and clinical development of these new therapies.

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Author information

Authors and Affiliations

  1. Onkologie und Hämatologie, Uniklinik-Dresden, Fetscherstr. 74, Haus 27, 01307, Dresden, Deutschland

    C. Grüllich

  2. Immunoanalytics- Research Group Tissue Control of Immunocytes, Helmholtz Zentrum München, München, Deutschland

    E. Nößner

  3. Klinik für Urologie, Uro-Onkologie, spezielle urologische und roboter-assistierte Chirurgie, Universitätsklinikum Köln, Köln, Deutschland

    D. Pfister

  4. Westdeutsches Tumorzentrum, Innere Klinik (Tumorforschung) und Klinik für Urologie, Universitätsklinikum Essen (AöR), Essen, Deutschland

    V. Grünwald

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  4. V. Grünwald
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Correspondence to C. Grüllich.

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Interessenkonflikt

C. Grüllich: Beratertätigkeit für BMS, MSD, Pfizer, Ipsen, Eisai, Astra Zeneca. E. Nößner: Beratertätigkeit für Roche, Definiens GmbH, IPSEN, Astrazeneca; Vortragstätigkeit für: Roche, Hexal, Novartis; Forschungsunterstützung: Phio Pharmaceuticals Corp, Medigene GmbH. V. Grünwald : Beratertätigkeit für Pfizer, Novartis, Bristol Myer Squibb, Ipsen, Eisai, EUSAPharm, MSD, Merck Serono, Lilly und Roche. Aktienbesitz Astra Zeneca, BMS, MSD. Forschungsförderung: Bristol Myer Squibb, MSD, AstraZeneca, Pfizer und Novartis. Vortragstätigkeit für: AstraZeneca, Pfizer, Novartis, Bristol Myer Squibb, MSD, Ipsen, Eisai, Lilly und Roche. D. Pfister : Beratertätigkeit für Sanofi, Janssen, MSD, Bayer, Vortragstätigkeit für: Sanofi, Janssen, Bayer, Ipsen, Roche.

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

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Grüllich, C., Nößner, E., Pfister, D. et al. Molekulare zielgerichtete Therapie und Immuntherapie des Prostatakarzinoms. Urologe 59, 687–694 (2020). https://doi.org/10.1007/s00120-020-01198-6

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