Deciphering the Role of PI3K/Akt/mTOR Pathway in Breast Cancer Biology and Pathogenesis

被引：114

作者：

McAuliffe, Priscilla F. ^{[3
]}

Meric-Bernstam, Funda ^{[3
]}

Mills, Gordon B. ^{[2
]}

Gonzalez-Angulo, Ana M. ^{[1
,2
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA

来源：

CLINICAL BREAST CANCER | 2010年 / 10卷

关键词：

HER2; Mammalian target of rapamycin; Phosphatidylinositol; 3-kinase; PTEN; RAPAMYCIN KINASE INHIBITOR; TUMOR-SUPPRESSOR GENE; PROTEIN S6 KINASE; MAMMALIAN TARGET; TRASTUZUMAB RESISTANCE; PHASE-II; TEMSIROLIMUS CCI-779; AKT PHOSPHORYLATION; ANTITUMOR-ACTIVITY; PIK3CA MUTATIONS;

D O I：

10.3816/CBC.2010.s.013

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway mediates multiple cellular functions critical to tumor initiation, progression, and outcomes, including growth and proliferation, metabolism, motility, migration, invasion, angiogenesis, survival, and autophagy. Tight regulation of this pathway is paramount to ensure that multiple cellular inputs are integrated for appropriate cellular outcomes. Frequent deregulation and aberrations of this pathway have been implicated in breast cancer development and progression. This review focuses on the biology of this pathway and its role in breast cancer pathogenesis. The role of therapies directed at targeting mTOR in the PI3K/Akt/mTOR pathway, which are currently being evaluated in clinical trials, will also be reviewed.

引用

页码：S59 / S65

页数：7

共 83 条

[1]

Agarwal R, 2010, CURR OPIN INVEST DR, V11, P615

[2] Comparison of Akt/mTOR signaling in primary breast tumors and matched distant metastases [J].

Akcakanat, Argun ;

Sahin, Aysegul ;

Shaye, Alexandra N. ;

Velasco, Marco A. ;

Meric-Bernstam, Funda .

CANCER, 2008, 112 (11) :2352-2358

[3] Rapamycin regulates the phosphorylation of rictor [J].

Akcakanat, Argun ;

Singh, Gopal ;

Hung, Mien-Chie ;

Meric-Bernstam, Funda .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2007, 362 (02) :330-333

[4] Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma [J].

Atkins, MB ;

Hidalgo, M ;

Stadler, WM ;

Logan, TF ;

Dutcher, JP ;

Hudes, GR ;

Park, Y ;

Lion, SH ;

Marshall, B ;

Boni, JP ;

Dukart, G ;

Sherman, ML .

JOURNAL OF CLINICAL ONCOLOGY, 2004, 22 (05) :909-918

[5] The PIK3CA gene is mutated with high frequency in human breast cancers [J].

Bachman, KE ;

Argani, P ;

Samuels, Y ;

Silliman, N ;

Ptak, J ;

Szabo, S ;

Konishi, H ;

Karakas, B ;

Blair, BG ;

Lin, C ;

Peters, BA ;

Velculescu, VE ;

Park, BH .

CANCER BIOLOGY & THERAPY, 2004, 3 (08) :772-775

[6] Different prognostic roles of mutations in the helical and kinase domains of the PIK3CA gene in breast carcinomas [J].

Barbareschi, Mattia ;

Buttitta, Fiamma ;

Felicioni, Lara ;

Cotrupi, Sabrina ;

Barassi, Fabio ;

Del Grammastro, Maela ;

Ferro, Antonella ;

Palma, Paolo Dalla ;

Galligioni, Enzo ;

Marchetti, Antonio .

CLINICAL CANCER RESEARCH, 2007, 13 (20) :6064-6069

[7] Detecting activation of ribosomal protein S6 kinase by complementary DNA and tissue microarray analysis [J].

Bärlund, M ;

Forozan, F ;

Kononen, J ;

Bubendorf, L ;

Chen, YD ;

Bittner, ML ;

Torhorst, J ;

Haas, P ;

Bucher, C ;

Sauter, G ;

Kallioniemi, OP ;

Kallioniemi, A .

JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2000, 92 (15) :1252-1259

[8] Phase II Randomized Study of Neoadjuvant Everolimus Plus Letrozole Compared With Placebo Plus Letrozole in Patients With Estrogen Receptor-Positive Breast Cancer [J].

Baselga, Jose ;

Semiglazov, Vladimir ;

van Dam, Peter ;

Manikhas, Alexey ;

Bellet, Meritxell ;

Mayordomo, Jose ;

Campone, Mario ;

Kubista, Ernst ;

Greil, Richard ;

Bianchi, Giulia ;

Steinseifer, Jutta ;

Molloy, Betty ;

Tokaji, Erika ;

Gardner, Humphrey ;

Phillips, Penny ;

Stumm, Michael ;

Lane, Heidi A. ;

Dixon, J. Michael ;

Jonat, Walter ;

Rugo, Hope S. .

JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (16) :2630-2637

[9] Akt-induced endocrine therapy resistance is reversed by inhibition of mTOR signaling [J].

Beeram, M. ;

Tan, Q.-T. N. ;

Tekmal, R. R. ;

Russell, D. ;

Middleton, A. ;

deGraffenried, L. A. .

ANNALS OF ONCOLOGY, 2007, 18 (08) :1323-1328

[10] A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer [J].

Berns, Katrien ;

Horlings, Hugo M. ;

Hennessy, Bryan T. ;

Madiredjo, Mandy ;

Hijmans, E. Marielle ;

Beelen, Karin ;

Linn, Sabine C. ;

Gonzalez-Angulo, Ana Maria ;

Stemke-Hale, Katherine ;

Hauptmann, Michael ;

Beijersbergen, Roderick L. ;

Mills, Gordon B. ;

de Vijver, Marc J. van ;

Bernards, Rene .

CANCER CELL, 2007, 12 (04) :395-402

← 1 2 3 4 5 6 7 8 9 →