A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer

DSpace/Manakin Repository

A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer

Citable link to this page

 

 
Title: A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer
Author: Lunardi, Andrea; Ala, Ugo; Epping, Mirjam T.; Salmena, Leonardo; Clohessy, John G.; Webster, Kaitlyn A.; Wang, Guocan; Mazzucchelli, Roberta; Bianconi, Maristella; Stack, Edward C.; Lis, Rosina; Patnaik, Akash; Cantley, Lewis C.; Bubley, Glenn; Cordon-Cardo, Carlos; Gerald, William L.; Montironi, Rodolfo; Signoretti, Sabina; Loda, Massimo; Nardella, Caterina; Pandolfi, Pier Paolo

Note: Order does not necessarily reflect citation order of authors.

Citation: Lunardi, A., U. Ala, M. T. Epping, L. Salmena, J. G. Clohessy, K. A. Webster, G. Wang, et al. 2013. “A co-clinical approach identifies mechanisms and potential therapies for androgen deprivation resistance in prostate cancer.” Nature genetics 45 (7): 747-755. doi:10.1038/ng.2650. http://dx.doi.org/10.1038/ng.2650.
Full Text & Related Files:
Abstract: Here we report an integrated analysis that leverages data from treatment of genetic mouse models of prostate cancer along with clinical data from patients to elucidate new mechanisms of castration resistance. We show that castration counteracts tumor progression in a Pten-loss driven mouse model of prostate cancer through the induction of apoptosis and proliferation block. Conversely, this response is bypassed upon deletion of either Trp53 or Lrf together with Pten, leading to the development of castration resistant prostate cancer (CRPC). Mechanistically, the integrated acquisition of data from mouse models and patients identifies the expression patterns of XAF1-XIAP/SRD5A1 as a predictive and actionable signature for CRPC. Importantly, we show that combined inhibition of XIAP, SRD5A1, and AR pathways overcomes castration resistance. Thus, our co-clinical approach facilitates stratification of patients and the development of tailored and innovative therapeutic treatments.
Published Version: doi:10.1038/ng.2650
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3787876/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879681
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters