MP33-01 METASTATIC CASTRATION-RESISTANT PROSTATE CANCER REMAINS DEPENDENT ON ONCOGENIC DRIVERS IN PRIMARY TUMORS

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I (MP33)1 Sep 2021MP33-01 METASTATIC CASTRATION-RESISTANT PROSTATE CANCER REMAINS DEPENDENT ON ONCOGENIC DRIVERS IN PRIMARY TUMORS Seiji Arai, David Einstein, Kazuhiro Suzuki, Steven Balk, Adam Sowalsky, and Joshua Russo Seiji AraiSeiji Arai More articles by this author , David EinsteinDavid Einstein More articles by this author , Kazuhiro SuzukiKazuhiro Suzuki More articles by this author , Steven BalkSteven Balk More articles by this author , Adam SowalskyAdam Sowalsky More articles by this author , and Joshua RussoJoshua Russo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002042.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Localized prostate cancer (PC) can be curable, but metastatic recurrence is unfortunately common. Metastatic PC is initially sensitive to androgen receptor inhibition, but eventually becomes castration-resistant (mCRPC). Early use of more intensive therapies targeting androgen receptor and other oncogenic drivers may be more effective than in advanced mCRPC. However, as oncogenic alterations found in mCRPC are less frequent in treatment-naïve primary PC, analysis of primary tumors may not reveal targetable metastatic drivers that are subclonal in the primary tumor or acquired at metastatic sites. METHODS: We analyzed PC samples spanning one patient’s clinical course: diagnostic biopsies, pre-/post-enzalutamide metastatic biopsies, and rapid autopsy samples including a patient-derived xenograft (PDX). RESULTS: Consistent with mCRPC being driven by non-truncal alterations, we identified RB1 loss throughout mCRPC samples, but not in the primary tumor. However, we identified a truncal EGFR-activating mutation in the primary that was maintained in mCRPC samples and the PDX, and showed that the PDX responded to the EGFR inhibitor. CONCLUSIONS: Truncal alterations can drive advanced mCRPC, and suggest that earlier detection and targeting of these truncal alterations may be effective at halting disease progression. Source of Funding: Congressionally Directed Medical Research Program (CDMRP), Prostate Cancer Research Program (Physician Research Award W81XWH-17-1-0350, Early Investigator Award W81XWH-18-1-0531, Idea Development Awards W81XWH-18-1-0379 and W81XWH-20-1-0925), the Prostate Cancer Foundation (Young Investigator Award 18YOUN24), the Intramural Research Program of the NIH, National Cancer Institute (NIH P01 - CA163227, SPORE in Prostate Cancer P50 – CA090281, and NIH P20 – CA233255) © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e606-e606 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Seiji Arai More articles by this author David Einstein More articles by this author Kazuhiro Suzuki More articles by this author Steven Balk More articles by this author Adam Sowalsky More articles by this author Joshua Russo More articles by this author Expand All Advertisement Loading ...