Bedeutung der Androgenrezeptor-Spleißvariante AR-V7 für Prognose und Therapie des fortgeschrittenen Prostatakarzinoms

Zusammenfassung

Ein kürzlich entdeckter Mechanismus, welcher es Prostatakarzinomzellen ermöglicht, die Wirkung endokriner Therapien zu umgehen, ist die Synthese C-terminal verkürzter, konstitutiv aktiver Androgenrezeptor(AR)-Spleißvarianten (AR-V). Ohne eine funktionsfähige C-terminal gelegene Hormon- bzw. Ligandenbindedomäne sind viele AR-Vs unempfindlich gegenüber Therapien, welche sich gegen die Androgen-/Androgenrezeptor-Signalachse richten. Erste Studien weisen darauf hin, dass AR-V7, die häufigste AR-V-Form, ein vielversprechender prädiktiver Tumormarker sowie relevanter Selektionsmarker bei der Behandlung des fortgeschrittenen Prostatakarzinoms ist. Die vorliegende Übersicht skizziert jüngste Fortschritte bei der AR-V7 Diagnostik und präsentiert einen Überblick über derzeitig durchgeführte zielgerichtete AR-V7 Therapien.

Abstract

A recently discovered mechanism enabling prostate cancer cells to escape the effects of endocrine therapies consists in the synthesis of C-terminally truncated, constitutively active androgen receptor (AR) splice variants (AR-V). Devoid of a functional C-terminal hormone/ligand binding domain, various AR-Vs are insensitive to therapies targeting the androgen/AR signalling axis. Preliminary studies suggest that AR-V7, the most common AR-V, is a promising predictive tumour marker and a relevant selection marker for the treatment of advanced prostate cancer. This review critically outlines recent advances in AR-V7 diagnostics and presents an overview of current AR-V7 targeted therapies.

Schlüsselwörter

Androgenrezeptor-Spleißvarianten, Therapieresistenz, Progressionsmarker, zielgerichtete Therapien

Keywords

androgen receptor splice variants, therapy resistance, progression marker, targeted therapies

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