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

被引：522

作者：

Bluemn, Eric G. ^{[1
,2
]}

Coleman, Ilsa M. ^{[2
]}

Lucas, Jared M. ^{[2
]}

Coleman, Roger T. ^{[2
]}

Hernandez-Lopez, Susana ^{[2
]}

Tharakan, Robin ^{[2
]}

Bianchi-Frias, Daniella ^{[2
]}

Dumpit, Ruth F. ^{[2
]}

Kaipainen, Arja ^{[2
]}

Corella, Alexandra N. ^{[2
]}

Yang, Yu Chi ^{[2
]}

Nyquist, Michael D. ^{[2
]}

Mostaghel, Elahe ^{[1
,2
]}

Hsieh, Andrew C. ^{[1
,2
]}

Zhang, Xiaotun ^{[3
]}

Corey, Eva ^{[3
]}

Brown, Lisha G. ^{[3
]}

Nguyen, Holly M. ^{[3
]}

Pienta, Kenneth ^{[6
]}

Ittmann, Michael ^{[1
,7
]}

Schweizer, Michael

True, Lawrence D. ^{[4
]}

Wise, David ^{[5
]}

Rennie, Paul S. ^{[8
]}

Vessella, Robert L. ^{[3
]}

Morrissey, Colm ^{[3
]}

Nelson, Peter S. ^{[1
,2
,3
,4
]}

机构：

[1] Univ Washington, Dept Med, Seattle, WA 98195 USA

[2] Fred Hutchinson Canc Res Ctr, Div Human Biol & Clin Res, Mailstop D4-100,1100 Fairview Ave N, Seattle, WA 98109 USA

[3] Univ Washington, Dept Urol, 1959 NE Pacific St, Seattle, WA 98195 USA

[4] Univ Washington, Dept Pathol, Seattle, WA 98195 USA

[5] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[6] Johns Hopkins Univ, Baltimore, MD USA

[7] Baylor Coll Med, Houston, TX 77030 USA

[8] Vancouver Prostate Ctr, Vancouver, BC, Canada

来源：

CANCER CELL | 2017年 / 32卷 / 04期

关键词：

SMALL-CELL CARCINOMA; LINEAGE PLASTICITY; INCREASED SURVIVAL; MOUSE MODEL; IN-VIVO; ACTIVATION; IDENTIFICATION; METASTASIS; RESISTANCE; EXPRESSION;

D O I：

10.1016/j.ccell.2017.09.003

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. Pharmacological inhibitors of MAPK or FGFR repressed the growth of double-negative PCs in vitro and in vivo. Our results indicate that FGF/MAPK blockade may be particularly efficacious against mPCs with an AR-null phenotype.

引用

页码：474 / +

页数：22

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