Accession Number : AD1043346


Title :   Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer


Descriptive Note : Technical Report,15 Sep 2016,14 Sep 2017


Corporate Author : University of Arizona Tucson United States


Personal Author(s) : Kraft, Andrew


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1043346.pdf


Report Date : 01 Oct 2017


Pagination or Media Count : 12


Abstract : There is an urgent need to develop both new approaches to the treatment of prostate cancer. Analysis of human prostate samples demonstrates that a specific signaling pathway, the Pim kinase pathway is elevated in the fibroblasts from human prostate tumors. To understand the role of myofibroblast/cancer associated fibroblasts (CAFs) in transformation, the laboratory proposes (1) to examine in detail the proteins secreted by the stroma that can modulate epithelial growth, (2) to evaluate the ability of Pim inhibitors to block this activity, and (3) to investigate whether exosomes can potentially be used as a biomarker of Pim kinase inhibitor activity. Results to date demonstrate that Pim increases in prostate stromal cells enhances protein synthesis, the levels of important transcription factors, long non-coding RNAs, and tyrosine kinases associated with signal transduction as well increased exosomal transfer both in cells co-cultured and when conditioned media is placed on prostate epithelial cells. These changes are blocked by the addition of Pim inhibitors. These results suggest that the Pim protein kinase can regulate stromal cell biology to modulate epithelial growth and that inhibitors of this protein kinase have the potential to block this process and thus inhibit tumor growth.


Descriptors :   PROSTATE CANCER , FIBROBLASTS , THERAPY , Inhibitors


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE