Targeting PI3K Signaling as a Therapeutic Approach for Colorectal Cancer

被引：111

作者：

Zhang, Jing ^{[1
,3
]}

Roberts, Thomas M. ^{[1
,3
]}

Shivdasani, Ramesh A. ^{[2
,4
]}

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA

[2] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[3] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA

[4] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

来源：

GASTROENTEROLOGY | 2011年 / 141卷 / 01期

关键词：

Colon Cancer; Neoplasm; Signal Transduction; Genetics; Tumor; ISLAND METHYLATOR PHENOTYPE; TYROSINE KINASE INHIBITORS; 3-KINASE CATALYTIC SUBUNIT; PIK3CA GENE-MUTATIONS; GROWTH IN-VITRO; PHOSPHOINOSITIDE; 3-KINASE; PHOSPHATIDYLINOSITOL; COLON-CANCER; MICROSATELLITE INSTABILITY; P110-ALPHA ISOFORM;

D O I：

10.1053/j.gastro.2011.05.010

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Survival times of patients with colorectal cancer (CRC) have increased over the past decade, primarily as a result of treatment with combinations of conventional cytotoxic agents. Because CRC is commonly associated with mutations in genes that control growth factor signaling, therapies are being developed to target the products of these genes; individualized treatment might also be guided by specific mutations in tumors and by new biomarkers. Currently, targeted therapies confer limited clinical benefit; better drugs are therefore needed. Genomic studies indicate that phosphoinositide 3-kinase (PI3K) signaling is one of the most frequently deregulated pathways in several human cancers, including CRC. PI3K signaling has an important role in cancer cell proliferation, survival, motility, and metabolism and therefore could be an attractive therapeutic target. We review PI3K signaling in CRC and discuss current therapeutic approaches.

引用

页码：50 / 61

页数：12

共 120 条

[91] Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer [J].

Souglakos, J. ;

Philips, J. ;

Wang, R. ;

Marwah, S. ;

Silver, M. ;

Tzardi, M. ;

Silver, J. ;

Ogino, S. ;

Hooshmand, S. ;

Kwak, E. ;

Freed, E. ;

Meyerhardt, J. A. ;

Saridaki, Z. ;

Georgoulias, V. ;

Finkelstein, D. ;

Fuchs, C. S. ;

Kulke, M. H. ;

Shivdasani, R. A. .

BRITISH JOURNAL OF CANCER, 2009, 101 (03) :465-472

[92] Microvascular patterning is controlled by fine-tuning the Akt signal [J].

Sun, JF ;

Phung, T ;

Shiojima, I ;

Felske, T ;

Upalakalin, JN ;

Feng, D ;

Kornaga, T ;

Dor, T ;

Dvorak, AM ;

Walsh, K ;

Benjamin, LE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (01) :128-133

[93] Depletion of PI3K p85α induces cell cycle arrest and apoptosis in colorectal cancer cells [J].

Sun, Yan ;

Zhao, Shiyi ;

Tian, Hua ;

Xie, Xiaoyun ;

Xiao, Faman ;

Li, Kang ;

Song, Yugang .

ONCOLOGY REPORTS, 2009, 22 (06) :1435-1441

[94] BRAF mutation, CpG island methylator phenotype and microsatellite instability occur more frequently and concordantly in mucinous than non-mucinous colorectal cancer [J].

Tanaka, H ;

Deng, GR ;

Matsuzaki, K ;

Kakar, S ;

Kim, GE ;

Miura, S ;

Sleisenger, MH ;

Kim, YS .

INTERNATIONAL JOURNAL OF CANCER, 2006, 118 (11) :2765-2771

[95] Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximab [J].

Tol, Jolien ;

Dijkstra, Jeroen R. ;

Klomp, Marjolein ;

Teerenstra, Steven ;

Dommerholt, Martin ;

Vink-Borger, M. Elisa ;

van Cleef, Patricia H. ;

van Krieken, J. Han ;

Punt, Cornelis J. A. ;

Nagtegaal, Iris D. .

EUROPEAN JOURNAL OF CANCER, 2010, 46 (11) :1997-2009

[96] The p110α isoform of phosphatidylinositol 3-kinase is essential for polyomavirus middle T antigen-mediated transformation [J].

Utermark, Tamara ;

Schaffhausen, Brian S. ;

Roberts, Thomas M. ;

Zhao, Jean J. .

JOURNAL OF VIROLOGY, 2007, 81 (13) :7069-7076

[97] 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

[98] The prevalence of PIK3CA mutations in gastric and colon cancer [J].

Velho, S ;

Oliveira, C ;

Ferreira, A ;

Ferreira, AC ;

Suriano, G ;

Schwartz, S ;

Duval, A ;

Carneiro, F ;

Machado, JC ;

Hamelin, R ;

Seruca, R .

EUROPEAN JOURNAL OF CANCER, 2005, 41 (11) :1649-1654

[99] BRAF, KRAS and PIK3CA mutations in colorectal serrated polyps and cancer:: Primary or secondary genetic events in colorectal carcinogenesis? [J].

Velho, Sergia ;

Moutinho, Catia ;

Cirnes, Luis ;

Albuquerque, Cristina ;

Hamelin, Richard ;

Schmitt, Fernando ;

Carneiro, Fatima ;

Oliveira, Carla ;

Seruca, Raquel .

BMC CANCER, 2008, 8 (1)

[100] PI3K p110β: More Tightly Controlled or Constitutively Active? [J].

Vogt, Peter K. .

MOLECULAR CELL, 2011, 41 (05) :499-501

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