Gene alterations in the PI3K/PTEN/AKT pathway as a mechanism of drug-resistance (Review)

被引：178

作者：

Hafsi, Sameh ^{[1
]}

Pezzino, Franca Maria ^{[1
]}

Candido, Saverio ^{[1
]}

Ligresti, Giovanni ^{[1
]}

Spandidos, Demetrios A. ^{[2
]}

Soua, Zohra ^{[3
]}

McCubrey, James A. ^{[4
]}

Travali, Salvatore ^{[1
]}

Libra, Massimo ^{[1
]}

机构：

[1] Univ Catania, Dept Biomed Sci, Pathol & Oncol Sect, Lab Translat Oncol & Funct Genom, I-95124 Catania, Italy

[2] Univ Crete, Dept Virol, Sch Med, Iraklion, Crete, Greece

[3] Univ Sousse, UR Mol Biol Leukemia & Lymphoma, Fac Med, Sousse, Tunisia

[4] E Carolina Univ, Dept Microbiol & Immunol, Brody Sch Med, Greenville, NC USA

来源：

INTERNATIONAL JOURNAL OF ONCOLOGY | 2012年 / 40卷 / 03期

关键词：

PIK3CA; gene mutations; PI3K pathway; AKT; cancer; TUMOR-SUPPRESSOR; PTEN FUNCTION; HUMAN CANCER; TRASTUZUMAB RESISTANCE; BREAST CANCERS; MUTATION; PIK3CA; GROWTH; CELLS; PTEN/MMAC1;

D O I：

10.3892/ijo.2011.1312

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

The most common therapeutic approach for many cancers is chemotherapy. However, many patients relapse after treatment due to the development of chemoresistance. Recently, targeted therapies represent novel approaches to destroy cancer cells. The PI3K/PTEN/AKT pathway is a key signaling pathway involved in the regulation of cell growth. Dysregulated signaling of this pathway may be associated with activating mutations of PI3K-related genes. Analyses of these mutations reveal that they increase the PI3K signal, stimulate downstream Akt signaling, promote growth factor-independent growth and increase cell invasion and metastasis. In this review, we summarize the PI3K/PTEN/AKT pathway genetic alterations in cancer and their potential clinical applications.

引用

收藏

页码：639 / 644

页数：6

相关论文

共 41 条

[1]

Mutational spectra of PTEN/MMAC1 gene: a tumor suppressor with lipid phosphatase activity [J].

Ali, IU ;

Schriml, LM ;

Dean, M .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1999, 91 (22) :1922-1932

[2]

Cancer-specific mutations in PIK3CA are oncogenic in vivo [J].

Bader, AG ;

Kang, SY ;

Vogt, PK .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (05) :1475-1479

[3]

MOLECULAR ALTERATIONS OF THE AKT2 ONCOGENE IN OVARIAN AND BREAST CARCINOMAS [J].

BELLACOSA, A ;

DEFEO, D ;

GODWIN, AK ;

BELL, DW ;

CHENG, JQ ;

ALTOMARE, DA ;

WAN, MH ;

DUBEAU, L ;

SCAMBIA, G ;

MASCIULLO, V ;

FERRANDINA, G ;

PANICI, PB ;

MANCUSO, S ;

NERI, G ;

TESTA, JR .

INTERNATIONAL JOURNAL OF CANCER, 1995, 64 (04) :280-285

[4]

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

[5]

PKB binding proteins: Getting in on the akt [J].

Brazil, DP ;

Park, J ;

Hemmings, BA .

CELL, 2002, 111 (03) :293-303

[6]

A transforming mutation in the pleckstrin homology domain of AKT1 in cancer [J].

Carpten, John D. ;

Faber, Andrew L. ;

Horn, Candice ;

Donoho, Gregory P. ;

Briggs, Stephen L. ;

Robbins, Christiane M. ;

Hostetter, Galen ;

Boguslawski, Sophie ;

Moses, Tracy Y. ;

Savage, Stephanie ;

Uhlik, Mark ;

Lin, Aimin ;

Du, Jian ;

Qian, Yue-Wei ;

Zeckner, Douglas J. ;

Tucker-Kellogg, Greg ;

Touchman, Jeffrey ;

Patel, Ketan ;

Mousses, Spyro ;

Bittner, Michael ;

Schevitz, Richard ;

Lai, Mei-Huei T. ;

Blanchard, Kerry L. ;

Thomas, James E. .

NATURE, 2007, 448 (7152) :439-U1

[7]

AKT2, A PUTATIVE ONCOGENE ENCODING A MEMBER OF A SUBFAMILY OF PROTEIN-SERINE THREONINE KINASES, IS AMPLIFIED IN HUMAN OVARIAN CARCINOMAS [J].

CHENG, JQ ;

GODWIN, AK ;

BELLACOSA, A ;

TAGUCHI, T ;

FRANKE, TF ;

HAMILTON, TC ;

TSICHLIS, PN ;

TESTA, JR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (19) :9267-9271

[8]

PTEN function in normal and neoplastic growth [J].

Chow, Lionel M. L. ;

Baker, Suzanne J. .

CANCER LETTERS, 2006, 241 (02) :184-196

[9]

Direct targets of phosphoinositide 3-kinase products in membrane traffic and signal transduction [J].

Corvera, S ;

Czech, MP .

TRENDS IN CELL BIOLOGY, 1998, 8 (11) :442-446

[10]

Cellular survival: a play in three Akts [J].

Datta, SR ;

Brunet, A ;

Greenberg, ME .

GENES & DEVELOPMENT, 1999, 13 (22) :2905-2927

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