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

[1] The AKT/IκB kinase pathway promotes angiogenic/metastatic gene expression in colorectal cancer by activating nuclear factor-κB and β-catenin [J].

Agarwal, A ;

Das, K ;

Lerner, N ;

Sathe, S ;

Cicek, M ;

Casey, G ;

Sizemore, N .

ONCOGENE, 2005, 24 (06) :1021-1031

[2] Mutations in the RAS-MAPK, PI(3)K (phosphatidylinositol-3-OH kinase) signaling network correlate with poor survival in a population-based series of colon cancers [J].

Barault, Ludovic ;

Veyrie, Nicolas ;

Jooste, Valerie ;

Lecorre, Delphine ;

Chapusot, Caroline ;

Ferraz, Jean-Marc ;

Lievre, Astrid ;

Cortet, Marion ;

Bouvier, Anne-Marie ;

Rat, Patrick ;

Roignot, Patrick ;

Faivre, Jean ;

Laurent-Puig, Pierre ;

Piard, Francoise .

INTERNATIONAL JOURNAL OF CANCER, 2008, 122 (10) :2255-2259

[3] A first-in-human phase I study of BKM120, an oral pan-class I PI3K inhibitor, in patients (pts) with advanced solid tumors [J].

Baselga, J. ;

De Jonge, M. J. ;

Rodon, J. ;

Burris, H. A., III ;

Birle, D. C. ;

De Buck, S. S. ;

Demanse, D. ;

Ru, Q. C. ;

Goldbrunner, M. ;

Bendell, J. C. .

JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (15)

[4]

Bendell J, 2011, P 102 ANN M AM ASS C, pLB

[5] A specific function for phosphatidylinositol 3-kinase α (p85α-p110α) in cell survival and for phosphatidylinositol 3-kinase β (p85α-p110β) in de novo DNA synthesis of human colon carcinoma cells [J].

Bénistant, C ;

Chapuis, H ;

Roche, S .

ONCOGENE, 2000, 19 (44) :5083-5090

[6] PIK3CA cancer mutations display gender and tissue specificity patterns [J].

Benvenuti, Silvia ;

Frattini, Milo ;

Arena, Sabrina ;

Zanon, Carlo ;

Cappelletti, Vera ;

Coradini, Danila ;

Daidone, Maria Grazia ;

Pilotti, Silvana ;

Pierotti, Marco A. ;

Bardelli, Alberto .

HUMAN MUTATION, 2008, 29 (02) :284-288

[7] PML inhibits HIF-1α translation and neoangiogenesis through repression of mTOR [J].

Bernardi, Rosa ;

Guernah, Ilhem ;

Jin, David ;

Grisendi, Silvia ;

Alimonti, Andrea ;

Teruya-Feldstein, Julie ;

Cordon-Cardo, Carlos ;

Simon, M. Celeste ;

Rafii, Shahin ;

Pandolfi, Pier Paolo .

NATURE, 2006, 442 (7104) :779-785

[8] Proliferative defect and embryonic lethality in mice homozygous for a deletion in the p110α subunit of phosphoinositide 3-kinase [J].

Bi, L ;

Okabe, I ;

Bernard, DJ ;

Wynshaw-Boris, A ;

Nussbaum, RL .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (16) :10963-10968

[9] Early embryonic lethality in mice deficient in the p110β catalytic subunit of PI 3-kinase [J].

Bi, L ;

Okabe, I ;

Bernard, DJ ;

Nussbaum, RL .

MAMMALIAN GENOME, 2002, 13 (03) :169-172

[10]

Boland CR, 2010, GASTROENTEROLOGY, V138, P2073, DOI [10.1053/j.gastro.2009.12.064, 10.1053/j.gastro.2010.04.024]

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