New paper below [1].
Some blue-skying from MD Anderson.
The current research focus continues to be androgen receptor [AR]-centric.
What if we accept that PCa is always going to find an escape path, & AR will continue to be involved in most cases?
"Given the difficulties in stopping all AR reactivation mechanisms, we propose that the identification of the driver signaling events downstream of the receptor offer viable, alternative therapeutic targets"
We are never going to see the end of this battle with the AR that Charles Huggins [2] started before I was even born.
It sounds like a good idea to me, but multiple pathways will have to be inhibited IMO.
-Patrick
[1] ncbi.nlm.nih.gov/pubmed/296...
Curr Opin Pharmacol. 2018 Mar 30;41:1-11. doi: 10.1016/j.coph.2018.03.002. [Epub ahead of print]
Delineation of the androgen-regulated signaling pathways in prostate cancer facilitates the development of novel therapeutic approaches.
Awad D1, Pulliam TL2, Lin C1, Wilkenfeld SR1, Frigo DE3.
Author information
1
Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA.
2
Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX, USA; Department of Biology and Biochemistry, University of Houston, Houston, TX, USA.
3
Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX, USA; Department of Biology and Biochemistry, University of Houston, Houston, TX, USA; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Molecular Medicine Program, The Houston Methodist Research Institute, Houston, TX, USA. Electronic address: frigo@mdanderson.org.
Abstract
Although androgen deprivation therapy (ADT) is initially effective for the treatment of progressive prostate cancer, it inevitably fails due to the onset of diverse resistance mechanisms that restore androgen receptor (AR) signaling. Thus, AR remains a desired therapeutic target even in the relapsed stages of the disease. Given the difficulties in stopping all AR reactivation mechanisms, we propose that the identification of the driver signaling events downstream of the receptor offer viable, alternative therapeutic targets. Here, we summarize recently described, AR-regulated processes that have been demonstrated to promote prostate cancer. By highlighting these signaling events and describing some of the ongoing efforts to pharmacologically modulate these pathways, our goal is to advocate potential new therapeutic targets that would represent an alternative approach for blocking AR actions.
PMID: 29609138 DOI: 10.1016/j.coph.2018.03.002
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