From Bedside to Bench. Maria Karlou 1 , Jun Yang2, Sankar Maity2, Nora M. Navone2, Jing-Fang Lu2, Xinhai Wan2, Anh Hoang1, Christopher J. Logothetis2, Eleni Efstathiou1 1 Department of Genitourinary Medical Oncology, David H. Koch Center for Applied Research of Genitourinary Cancers, The Stanford Alexander Tissue Derivatives Laboratory, The University of Texas MD Anderson Cancer Center, Houston, TX, Akt signaling pathway USA, 2 Department

of Genitourinary Medical Oncology, David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Background: In the tumor microenvironment, activation of tumor-stromal interactions is considered to play a critical role in Prostate Cancer (PCa) progression. LY3039478 mouse hedgehog signaling, a developmental pathway implicated in cancer, has been associated with resistance to cytotoxic treatment in human samples. Thus hedgehog signaling inhibition is a candidate therapeutic Salubrinal clinical trial target for combination with maximal androgen ablation. Selection of preclinical models of PCa relevant

to the human disease is imperative for development of applicable therapeutic strategies. Materials and methods: Xenografts generated by our research team from castrate-resistant PCa specimens were used to screen gene expression of key components in hedgehog signaling. Tumors were examined for the RNA and protein expression Tideglusib of Shh, Gli1, Gli2, Smo, Ptch1 and Sufu by Real Time RT-PCR and IHC in both (human) prostate cancer cells and in host (mouse) derived stromal cells. Results-Conclusions:

118b is an androgen independent xenograft, not expressing AR, inducing bone formation in the surrounding stroma. This xenograft has a striking overexpression of hedgehog signaling including nuclear expression of Gli1 and Gli2. Xenografts A10, 137, 117, 115 and 79 are expressing AR and some extent of hedgehog signaling. All studied models showed differential gene expression of hedgehog signaling components in stromal compartment compared to tumor cells. Notably, A10 when grown in castrate host has increased expression of the transcription factors Gli1 and Gli2 and the ligand Shh, in the stromal compartment as compared to growth in non-castrate (vide infra). This experiment recapitulates the human condition based on our translational results and therefore might be the most well suited model to test the effect of hedgehog signaling inhibition on blocking androgen-resistant growth. Poster No.