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

[1] A phase I/II, first-in-human dose-escalation study of GSK2636771 in patients (pts) with PTEN-deficient advanced tumors [J].

Arkenau, Hendrik-Tobias ;

Mateo, Joaquin ;

Lemech, Charlotte Rose ;

Infante, Jeffrey R. ;

Burris, Howard A. ;

Bang, Yung-Jue ;

Eder, Joseph Paul ;

Herbst, Roy S. ;

Sharma, Sunil ;

Chung, Hyun Cheol ;

Decordova, Shaun ;

Swales, Karen E. ;

Garrett, Michelle D. ;

Loftiss, Jill I. ;

Durante, Michael ;

Russo, Mark W. ;

Suttle, Benjamin B. ;

Motwani, Monica ;

Kumar, Rakesh ;

De Bono, Johann Sebastian .

JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (15)

[2] Glucocorticoid Receptor Confers Resistance to Antiandrogens by Bypassing Androgen Receptor Blockade [J].

Arora, Vivek K. ;

Schenkein, Emily ;

Murali, Rajmohan ;

Subudhi, Sumit K. ;

Wongvipat, John ;

Balbas, Minna D. ;

Shah, Neel ;

Cai, Ling ;

Efstathiou, Eleni ;

Logothetis, Chris ;

Zheng, Deyou ;

Sawyers, Charles L. .

CELL, 2013, 155 (06) :1309-1322

[3]

Beer TM, 2014, NEW ENGL J MED, V371, P424, DOI 10.1056/NEJMoa1405095

[4] Phase I, Dose-Escalation Study of BKM120, an Oral Pan-Class I PI3K Inhibitor, in Patients With Advanced Solid Tumors [J].

Bendell, Johanna C. ;

Rodon, Jordi ;

Burris, Howard A. ;

de Jonge, Maja ;

Verweij, Jaap ;

Birle, Diana ;

Demanse, David ;

De Buck, Stefan S. ;

Ru, Qinhua C. ;

Peters, Malte ;

Goldbrunner, Michael ;

Baselga, Jose .

JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (03) :282-290

[5] Androgen-induced differentiation and tumorigenicity of human prostate epithelial cells [J].

Berger, R ;

Febbo, PG ;

Majumder, PK ;

Zhao, JJ ;

Mukherjee, S ;

Signoretti, S ;

Campbell, KT ;

Sellers, WR ;

Roberts, TM ;

Loda, M ;

Golub, TR ;

Hahn, WC .

CANCER RESEARCH, 2004, 64 (24) :8867-8875

[6] The Master Neural Transcription Factor BRN2 Is an Androgen Receptor-Suppressed Driver of Neuroendocrine Differentiation in Prostate Cancer [J].

Bishop, Jennifer L. ;

Thaper, Daksh ;

Vahid, Sepideh ;

Davies, Alastair ;

Ketola, Kirsi ;

Kuruma, Hidetoshi ;

Jama, Randy ;

Nip, Ka Mun ;

Angeles, Arkhjamil ;

Johnson, Fraser ;

Wyatt, Alexander W. ;

Fazli, Ladan ;

Gleave, Martin E. ;

Lin, Dong ;

Rubin, Mark A. ;

Collins, Colin C. ;

Wang, Yuzhuo ;

Beltran, Himisha ;

Zoubeidi, Amina .

CANCER DISCOVERY, 2017, 7 (01) :54-71

[7] Targeting the PI3K/Akt/mTOR pathway in castration-resistant prostate cancer [J].

Bitting, Rhonda L. ;

Armstrong, Andrew J. .

[8] A multicenter phase 1 study of PX-866 in combination with docetaxel in patients with advanced solid tumours [J].

Bowles, D. W. ;

Ma, W. W. ;

Senzer, N. ;

Brahmer, J. R. ;

Adjei, A. A. ;

Davies, M. ;

Lazar, A. J. ;

Vo, A. ;

Peterson, S. ;

Walker, L. ;

Hausman, D. ;

Rudin, C. M. ;

Jimeno, A. .

BRITISH JOURNAL OF CANCER, 2013, 109 (05) :1085-1092

[9]

Burris HA, 2011, J Clin Oncol, V29, P3003, DOI DOI 10.1200/JCO.2011.29.15SUPPL.3003

[10] Reciprocal Feedback Regulation of PI3K and Androgen Receptor Signaling in PTEN-Deficient Prostate Cancer [J].

Carver, Brett S. ;

Chapinski, Caren ;

Wongvipat, John ;

Hieronymus, Haley ;

Chen, Yu ;

Chandarlapaty, Sarat ;

Arora, Vivek K. ;

Le, Carl ;

Koutcher, Jason ;

Scher, Howard ;

Scardino, Peter T. ;

Rosen, Neal ;

Sawyers, Charles L. .

CANCER CELL, 2011, 19 (05) :575-586

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