Zusammenfassung
In der modernen Onkologie ist das molekulare Tumorboard die Schnittstelle zwischen Klinik und Grundlagenforschung. Durch die interdisziplinäre Zusammenarbeit von Experten verschiedener Fachdisziplinen soll die Indikation zur molekularbiologischen Tumoranalysen sinnvoll gestellt, die Untersuchungsergebnisse korrekt interpretiert und hierauf basierende personalisierte Therapieempfehlungen ausgegeben werden. Bezogen auf das metastasierte Prostatakarzinom können hiervon insbesondere Patienten mit familiärem Prostatakarzinom, jungen Manifestationsalter oder nach Ausschöpfung von zugelassenen Standardtherapien profitieren. Mit der Androgenrezeptor-Splicevariante 7 (AR-V7) steht ein prädiktiver Marker für das Ansprechen auf eine Hormontherapie mit Abirateron oder Enzalutamid zur Verfügung. Testverfahren zur Bestimmung des AR-V7-Status im Blut sind bereits kommerziell erwerblich. Mutationen in den DNA-Reparaturmechanismen stellen einen weiteren Ansatzpunkt für zielgerichtete, personalisierte Therapien dar. Defekte in der homologen Rekombination erhöhen die Empfindlichkeit von Tumorzellen gegenüber Poly(ADP-Ribose)-Polymerase-(PARP-)Inhibitoren wie Olaparib. In der TOPARP-A-Studie, eine Phase-II-Studie, lag die Ansprechrate bei Patienten mit metastasiertem Prostatakarzinom und Mutationen in DNA-Reparaturgenen bei 88 %. Mikrosatelliteninstabilität ist die Folge von Defekten in der DNA-Mismatch-Reparatur. Mit dem Immun-Checkpoint-Inhibitor Pembrolizumab steht auch für diese Patientenkollektiv eine wirksame Therapie zur Verfügung. Da weder PARP-Inhibitoren noch Pembrolizumab aktuell zur Therapie des metastasierten Prostatakarzinoms in Deutschland zugelassen sind, stärkt die Empfehlung eines molekularen Tumorboards die Erfolgsaussichten für die Genehmigung eines individuellen Heilversuches durch die Krankenkassen.
Abstract
In modern oncology, molecular tumor boards are the interface between the public healthcare system and clinical research institutions. An interdisciplinary team of medical and scientific experts assesses if extensive molecular testing for tumor profiling is appropriate and discusses therapeutic options for patients with newly diagnosed treatable alterations. In the field of metastatic prostate cancer, patients especially with a strong family history, young age of diagnosis and those who have exhausted standard treatments may benefit from molecular profiling. Expression of the androgen receptor splice variant 7 (AR-V7) predicts nonresponse to next-generation AR-directed therapy like abiraterone or enzalutamide. Different blood tests for AR-V7 detection are now commercially available. Mutations in the DNA repair pathway are another frequent event in metastatic prostate cancer. Homologous recombination defects sensitize cancer cells to poly(ADP-ribose) polymerase (PARP) inhibitors. In the TOPARP-A trial, the PARP inhibitor olaparib led to high response rates (88%) in patients with mutated DNA repair genes. Furthermore, patients with DNA mismatch repair deficiency and/or microsatellite instability seem to benefit from PD-1 inhibitors, particularly pembrolizumab. At this time neither PARP inhibitors nor PD-1 inhibitors are approved for metastatic prostate cancer treatment in Germany. Therefore, a recommendation of a molecular tumor board for biomarker-matched off-label use of approved drugs across entity barriers will support coverage by health insurance.
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A.K. Seitz, M.M. Heck, M.W. Kamer und C. Grüllich geben an, dass kein Interessenkonflikt besteht.
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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Seitz, A.K., Heck, M.M., Kamer, M.W. et al. Molekulares Tumorboard Prostatakarzinom. Urologe 58, 752–759 (2019). https://doi.org/10.1007/s00120-019-0933-2
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DOI: https://doi.org/10.1007/s00120-019-0933-2
Schlüsselwörter
- Zielgerichtete Tumortherapie
- Androgenrezeptor
- Hormontherapie
- Programmed cell death inhibitor
- Poly(-ADP-Ribose‑)Polymerase