Oncolytic Herpes Simplex Virus and PI3K Inhibitor BKM120 Synergize to Promote Killing of Prostate Cancer Stem-like Cells.

Oncolytic Herpes Simplex Virus and PI3K Inhibitor BKM120 Synergize to Promote Killing of Prostate Cancer Stem-like Cells. Mol Ther Oncolytics. 2019 Jun 28;13:58-66 Authors: Wang L, Ning J, Wakimoto H, Wu S, Wu CL, Humphrey MR, Rabkin SD, Martuza RL Abstract Novel therapies to override chemo-radiation resistance in prostate cancer (PCa) are needed. Prostate cancer sphere-forming cells (PCSCs) (also termed prostate cancer stem-like cells) likely participate in tumor progression and recurrence, and they are important therapeutic targets. We established PCSC-enriched spheres by culturing human (DU145) and murine (TRAMP-C2) PCa cells in growth factor-defined serum-free medium, and we characterized stem-like properties of clonogenicity and tumorigenicity. The efficacy of two different oncolytic herpes simplex viruses (oHSVs) (G47Δ and MG18L) in PCSCs was tested alone and in combination with radiation; chemotherapy; and inhibitors of phosphoinositide 3-kinase (PI3K), Wnt, and NOTCH in vitro; and, G47Δ was tested with the PI3K inhibitor BKM120 in a PCSC-derived tumor model in vivo. PCSCs were more tumorigenic than serum-cultured parental cells. Human and murine PCSCs were sensitive to oHSV and BKM120 killing in vitro, while the combination was synergistic. oHSV combined with radiation, docetaxel, Wnt, or NOTCH inhibitors was not. In athymic mice bearing DU145 PCSC-derived tumors, the combination of intra-tumoral G47Δ and systemic BKM1...
Source: Herpes - Category: Infectious Diseases Authors: Tags: Mol Ther Oncolytics Source Type: research