AR Signaling and the PI3K Pathway in Prostate Cancer

被引：145

作者：

Crumbaker, Megan ^{[1
,2
]}

Khoja, Leila ^{[3
,4
]}

Joshua, Anthony M. ^{[1
,2
,5
]}

机构：

[1] St Vincents Hosp, Kinghorn Canc Ctr, 370 Victoria St, Sydney, NSW 2010, Australia

[2] Univ New South Wales, St Vincents Clin Sch, Garvan Inst Med Res, 384 Victoria St, Sydney, NSW 2010, Australia

[3] AstraZeneca UK, Clin Discovery Unit, Early Clin Dev Innovat Med, da Vinci Bldg,Melbourn Sci Pk, Melbourn SG8 6HB, Herts, England

[4] Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Cambridge Biomed Campus,Hills Rd, Cambridge CB2 0QQ, England

[5] Univ Toronto, Univ Hlth Network, Princess Margaret Canc Ctr, Univ Ave, Toronto, ON M5G 2M9, Canada

来源：

CANCERS | 2017年 / 9卷 / 04期

关键词：

PI3K; prostate cancer; AR signaling; castrate resistant prostate cancer; ANDROGEN RECEPTOR VARIANTS; PHASE-II TRIAL; TUMOR-SUPPRESSOR; ABIRATERONE ACETATE; INCREASED SURVIVAL; CATALYTIC SUBUNIT; GROWTH-INHIBITION; SPLICE VARIANTS; DOSE-ESCALATION; PATIENTS PTS;

D O I：

10.3390/cancers9040034

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Prostate cancer is a leading cause of cancer-related death in men worldwide. Aberrant signaling in the androgen pathway is critical in the development and progression of prostate cancer. Despite ongoing reliance on androgen receptor (AR) signaling in castrate resistant disease, in addition to the development of potent androgen targeting drugs, patients invariably develop treatment resistance. Interactions between the AR and PI3K pathways may be a mechanism of treatment resistance and inhibitors of this pathway have been developed with variable success. Herein we outline the role of the PI3K pathway in prostate cancer and, in particular, its association with androgen receptor signaling in the pathogenesis and evolution of prostate cancer, as well as a review of the clinical utility of PI3K targeting.

引用

页数：15

共 107 条

[91] Ligand-independent activation of the androgen receptor by interleukin-6 and the role of steroid receptor coactivator-1 in prostate cancer cells [J].

Ueda, T ;

Mawji, NR ;

Bruchovsky, N ;

Sadar, MD .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (41) :38087-38094

[92] Changes in androgen receptor nongenotropic signaling correlate with transition of LNCaP cells to androgen independence [J].

Unni, E ;

Sun, SH ;

Nan, BC ;

McPhaul, MJ ;

Cheskis, B ;

Mancini, MA ;

Marcelli, M .

CANCER RESEARCH, 2004, 64 (19) :7156-7168

[93] AKT-Independent Signaling Downstream of Oncogenic PIK3CA Mutations in Human Cancer [J].

Vasudevan, Krishna M. ;

Barbie, David A. ;

Davies, Michael A. ;

Rabinovsky, Rosalia ;

McNear, Chontelle J. ;

Kim, Jessica J. ;

Hennessy, Bryan T. ;

Tseng, Hsiuyi ;

Pochanard, Panisa ;

Kim, So Young ;

Dunn, Ian F. ;

Schinzel, Anna C. ;

Sandy, Peter ;

Hoersch, Sebastian ;

Sheng, Qing ;

Gupta, Piyush B. ;

Boehm, Jesse S. ;

Reiling, Jan H. ;

Silver, Serena ;

Lu, Yiling ;

Stemke-Hale, Katherine ;

Dutta, Bhaskar ;

Joy, Corwin ;

Sahin, Aysegul A. ;

Gonzalez-Angulo, Ana Maria ;

Lluch, Ana ;

Rameh, Lucia E. ;

Jacks, Tyler ;

Root, David E. ;

Lander, Eric S. ;

Mills, Gordon B. ;

Hahn, William C. ;

Sellers, William R. ;

Garraway, Levi A. .

CANCER CELL, 2009, 16 (01) :21-32

[94] The phosphatidylinositol 3-kinase-AKT pathway in human cancer [J].

Vivanco, I ;

Sawyers, CL .

NATURE REVIEWS CANCER, 2002, 2 (07) :489-501

[95] Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer [J].

Wang, SY ;

Gao, J ;

Lei, QY ;

Rozengurt, N ;

Pritchard, C ;

Jiao, J ;

Thomas, GV ;

Li, G ;

Roy-Burman, P ;

Nelson, PS ;

Liu, X ;

Wu, H .

CANCER CELL, 2003, 4 (03) :209-221

[96] Biologic and clinical significance of androgen receptor variants in castration resistant prostate cancer [J].

Ware, Kathryn E. ;

Garcia-Blanco, Mariano A. ;

Armstrong, Andrew J. ;

Dehm, Scott M. .

[97] Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer [J].

Watson, Philip A. ;

Arora, Vivek K. ;

Sawyers, Charles L. .

NATURE REVIEWS CANCER, 2015, 15 (12) :701-711

[98] PTEN-deficient cancers depend on PIK3CB [J].

Wee, Susan ;

Wiederschain, Dmitri ;

Maira, Sauveur-Michel ;

Loo, Alice ;

Miller, Christine ;

DeBeaumont, Rosalie ;

Stegmeier, Frank ;

Yao, Yung-Mae ;

Lengauer, Christoph .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (35) :13057-13062

[99]

Whitacre DC, 2002, CELL GROWTH DIFFER, V13, P1

[100]

Yadav N, 2012, MINERVA UROL NEFROL, V64, P35

← 2 3 4 5 6 7 8 9 10 11 →