Androgen Receptor Pathway-Independent Prostate Cancer Is Sustained through FGF Signaling

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Cancer Cell
October 9, 2017

Eric G. Bluemn, Ilsa M. Coleman, Jared M. Lucas, Roger T. Coleman, Susana Hernandez-Lopez, Robin Tharakan, Daniella Bianchi-Frias, Ruth F. Dumpit, Arja Kaipainen, Alexandra N. Corella, Yu Chi Yang, Michael D. Nyquist, Elahe Mostaghel, Andrew C. Hsieh, Xiaotun Zhang, Eva Corey, Lisha G. Brown, Holly M. Nguyen, Kenneth Pienta, Michael Ittmann, Michael Schweizer, Lawrence D. True, David Wise, Paul S. Rennie, Robert L. Vessella, Colm Morrissey, Peter S. Nelson

Androgen receptor (AR) signaling is a distinctive feature of prostate carcinoma (PC) and represents the major therapeutic target for treating metastatic prostate cancer (mPC). Though highly effective, AR antagonism can produce tumors that bypass a functional requirement for AR, often through neuroendocrine (NE) transdifferentiation. Through the molecular assessment of mPCs over two decades, we find a phenotypic shift has occurred in mPC with the emergence of an AR-null NE-null phenotype. These “double-negative” PCs are notable for elevated FGF and MAPK pathway activity, which can bypass AR dependence. 

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