Targeting the PI3K/Akt/mTOR Pathway for Breast Cancer Therapy

被引：89

作者：

Cidado, Justin ^{[1
]}

Park, Ben Ho ^{[1
]}

机构：

[1] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21287 USA

来源：

JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA | 2012年 / 17卷 / 3-4期

关键词：

PI3; Kinase; PIK3CA; Breast cancer; Targeted therapy; PROTEIN-KINASE-B; PHOSPHATIDYLINOSITOL 3-KINASE INHIBITOR; PIK3CA MUTATIONS; PHOSPHOINOSITIDE; 3-KINASE; TUMOR-SUPPRESSOR; METASTATIC-DISEASE; SIGNALING PATHWAY; COWDEN-DISEASE; HIGH-FREQUENCY; PI3K PATHWAY;

D O I：

10.1007/s10911-012-9264-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Recent advances in genetics and genomics have revealed new pathways that are aberrantly activated in many breast cancers. Chief among these genetic changes are somatic mutations and/or gains and losses of key genes within the phosphoinositide 3-kinase (PI3K) pathway. Since breast cancer cell growth and progression is often dependent upon activation of the PI3K pathway, there has been intense research interest in finding therapeutic agents that can selectively inhibit one or more constituents of this signaling cascade. Here we review key molecules involved with aberrant PI3K pathway activation in breast cancers and current efforts to target these components for therapeutic gain.

引用

页码：205 / 216

页数：12

共 130 条

[1] Prediction of adjuvant chemotherapy benefit in endocrine responsive, early breast cancer using multigene assays [J].

Albain, Kathy S. ;

Paik, Soonmyung ;

van't Veer, Laura .

BREAST, 2009, 18 :S141-S145

[2] Mechanism of activation of protein kinase B by insulin and IGF-1 [J].

Alessi, DR ;

Andjelkovic, M ;

Caudwell, B ;

Cron, P ;

Morrice, N ;

Cohen, P ;

Hemmings, BA .

EMBO JOURNAL, 1996, 15 (23) :6541-6551

[3] Prospective Study Evaluating the Impact of Tissue Confirmation of Metastatic Disease in Patients With Breast Cancer [J].

Amir, Eitan ;

Miller, Naomi ;

Geddie, William ;

Freedman, Orit ;

Kassam, Farrah ;

Simmons, Christine ;

Oldfield, Maria ;

Dranitsaris, George ;

Tomlinson, George ;

Laupacis, Andreas ;

Tannock, Ian F. ;

Clemons, Mark .

JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (06) :587-592

[4]

[Anonymous], N ENGL J MED

[5] WORTMANNIN IS A POTENT PHOSPHATIDYLINOSITOL 3-KINASE INHIBITOR - THE ROLE OF PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE IN NEUTROPHIL RESPONSES [J].

ARCARO, A ;

WYMANN, MP .

BIOCHEMICAL JOURNAL, 1993, 296 :297-301

[6] 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

[7] PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2 [J].

Balendran, A ;

Casamayor, A ;

Deak, M ;

Paterson, A ;

Gaffney, P ;

Currie, R ;

Downes, CP ;

Alessi, DR .

CURRENT BIOLOGY, 1999, 9 (08) :393-404

[8] Targeting the Phosphoinositide-3 (PI3) Kinase Pathway in Breast Cancer [J].

Baselga, Jose .

ONCOLOGIST, 2011, 16 :12-19

[9] Rapamycin passes the torch: a new generation of mTOR inhibitors [J].

Benjamin, Don ;

Colombi, Marco ;

Moroni, Christoph ;

Hall, Michael N. .

NATURE REVIEWS DRUG DISCOVERY, 2011, 10 (11) :868-880

[10] Rapamycin blocks the phosphorylation of 4E-BP1 and inhibits cap-dependent initiation of translation [J].

Beretta, L ;

Gingras, AC ;

Svitkin, YV ;

Hall, MN ;

Sonenberg, N .

EMBO JOURNAL, 1996, 15 (03) :658-664

← 1 2 3 4 5 6 7 8 9 10 →