Abstract B035: Radio-resistance of PTEN-deficient prostate tumors is enhanced by treatment-induced chemokine signaling and is associated with biochemical recurrence and development of metastasis

Copy number alterations of the tumor-suppressor gene PTEN occur frequently in primary prostate cancer and are prognostic for relapse post-radiotherapy (RT). Preclinical modelling supports elevated CXC-chemokine signaling as a critical mediator of PTEN-depleted disease progression, and therapeutic resistance. Our objective was to establish the correlation of PTEN-deficiency with CXC-chemokine signaling and its association with clinical outcome following RT. Techniques employed included gene cluster and survival analysis of prostate cancer datasets; in vitro biologic assays extending to RT-PCR, immunoblotting, clonogenic survival assays and flow cytometry; and the use of two in vivo PTEN-deficient xenograft models. Analysis of gene expression data from the MSKCC cohort characterized a PTENLOW/CXCR1HIGH/CXCR2HIGH cluster of tumors that associates with earlier time to biochemical recurrence (HR 5.87, p 90 months). Kaplan-Meier analysis confirmed that PTENLOW/CXCR1HIGH/CXCR2HIGH tumors were associated with a significantly reduced time to biochemical recurrence (HR 2.65, p Citation Format: Chris W.D. Armstrong, Jonathan A. Coulter, Chee Wee Ong, Pamela J. Maxwell, Karl T. Butterworth, Oksana Lyubomska, Melissa J. LaBonte, Silvia Berlingeri, Rebecca Gallagher, Steven M. Walker, Joe M. O’Sullivan, Suneil Jain, Ian G. Mills, Manuel Salto-Tellez, Timothy Illidge, Richard D. Kennedy, Kevin M. Prise, David J.J. Waugh. Radio-resistance of PTEN-deficient prostate tumors is enhanced by treatment-induced chemokine signaling and is associated with biochemical recurrence and development of metastasis [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B035.