Targeting a Novel Androgen Receptor-Repressed Pathway in Prostate Cancer Therapy
Technical Report,01 Sep 2018,31 Aug 2019
University of Pittsburgh Pittsburgh United States
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The central hypothesis of the proposal is that PKD plays a crucial role in limiting the effectiveness of ADT by increasing prostate cancer survival through upregulating AURKA expression. AURKA encodes the protein Aurora A kinase, which is a master cell cycle regulator that is often dysregulated in human cancers. Our data demonstrated an important role of PKD in regulating Aurora A stability, implying that PKDs role in cancer cell survival and proliferation may be mediated through Aurora A. The primary goal of this study is to investigate the potential roles of PKD in mediating therapeutic resistance to ADT and to investigate the impact of PKD SMI-based combination therapies to curtail ADT-induced therapy resistance. This remains our main focus during the third funding cycle. Major efforts were devoted to Aim 3, where we seek to determine the functional input of PKD in ADT resistance invivo and assess the efficacy of PKD SMI in combination with AR antagonists in prostate cancer mouse models. The work is still on-going since the animal studies take longer time to complete. We have two manuscripts under preparation. A 6-month extension of this project has been approved.
- Medicine and Medical Research