Development of Phosphoinositide-3 Kinase Pathway Inhibitors for Advanced Cancer

被引：56

作者：

Cleary, James M. ^{[1
]}

Shapiro, Geoffrey I. ^{[1
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Early Drug Dev Ctr, Boston, MA 02115 USA

来源：

CURRENT ONCOLOGY REPORTS | 2010年 / 12卷 / 02期

关键词：

Phosphoinositide-3; kinase; Targeted therapy; Drug development; CELL-PROLIFERATION; P110-DELTA ISOFORM; LUNG-CANCER; 3-KINASE; PI3K; RESISTANCE; GROWTH; MUTATIONS; INDUCTION; APOPTOSIS;

D O I：

10.1007/s11912-010-0091-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The phosphoinositide-3 kinase (PI3K) pathway plays a critical role in cancer cell growth and survival. PI3K is activated in human cancers by elevated receptor tyrosine kinase activity, RAS mutation, as well as by mutation, amplification, and deletion of genes encoding components of the pathway. Additionally, PI3K pathway activation plays an important role in acquired resistance to both chemotherapy and targeted agents. The essential role of PI3K in human cancer has led to the development of PI3K pathway inhibitors that have shown promise in preclinical models and have entered phase 1 clinical trials. This article reviews preclinical and clinical data on members of this novel drug class, as well as data justifying the combination of PI3K inhibitors with other anticancer agents.

引用

页码：87 / 94

页数：8

共 54 条

[1] The survival kinases Akt and Pim as potential pharmacological targets [J].

Amaravadi, R ;

Thompson, CB .

JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (10) :2618-2624

[2]

[Anonymous], 2009, J CLIN ONCOL S

[3] A selective inhibitor of the p110δ isoform of PI 3-kinase inhibits AML cell proliferation and survival and increases the cytotoxic effects of VP16 [J].

Billottet, C. ;

Grandage, V. L. ;

Gale, R. E. ;

Quattropani, A. ;

Rommel, C. ;

Vanhaesebroeck, B. ;

Khwaja, A. .

ONCOGENE, 2006, 25 (50) :6648-6659

[4] Specific apoptosis induction by the dual PI3K/mTor inhibitor NVP-BEZ235 in HER2 amplified and PIK3CA mutant breast cancer cells [J].

Brachmann, Saskia M. ;

Hofmann, Irmgard ;

Schnell, Christian ;

Fritsch, Christine ;

Wee, Susan ;

Lane, Heidi ;

Wang, Shaowen ;

Garcia-Echeverria, Carlos ;

Maira, Sauveur-Michel .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (52) :22299-22304

[5] 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

[6] The PTEN-PI3K pathway: of feedbacks and cross-talks [J].

Carracedo, A. ;

Pandolfi, P. P. .

ONCOGENE, 2008, 27 (41) :5527-5541

[7] Phosphatidylinositol 3-Kinase Hyperactivation Results in Lapatinib Resistance that Is Reversed by the mTOR/Phosphatidylinositol 3-Kinase Inhibitor NVP-BEZ235 [J].

Eichhorn, Pieter J. A. ;

Gili, Magui ;

Scaltriti, Maurizio ;

Serra, Violeta ;

Guzman, Marta ;

Nijkamp, Wouter ;

Beijersbergen, Roderick L. ;

Valero, Vanesa ;

Seoane, Joan ;

Bernards, Rene ;

Baselga, Jose .

CANCER RESEARCH, 2008, 68 (22) :9221-9230

[8] MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling [J].

Engelman, Jeffrey A. ;

Zejnullahu, Kreshnik ;

Mitsudomi, Tetsuya ;

Song, Youngchul ;

Hyland, Courtney ;

Park, Joon Oh ;

Lindeman, Neal ;

Gale, Christopher-Michael ;

Zhao, Xiaojun ;

Christensen, James ;

Kosaka, Takayuki ;

Holmes, Alison J. ;

Rogers, Andrew M. ;

Cappuzzo, Federico ;

Mok, Tony ;

Lee, Charles ;

Johnson, Bruce E. ;

Cantley, Lewis C. ;

Janne, Pasi A. .

SCIENCE, 2007, 316 (5827) :1039-1043

[9] Allelic dilution obscures detection of a biologically significant resistance mutation in EGFR-amplified lung cancer [J].

Engelman, Jeffrey A. ;

Mukohara, Toru ;

Zejnullahu, Kreshnik ;

Lifshits, Eugene ;

Borras, Ana M. ;

Gale, Christopher-Michael ;

Naumov, George N. ;

Yeap, Beow Y. ;

Jarrell, Emily ;

Sun, Jason ;

Tracy, Sean ;

Zhao, Xiaojun ;

Heymach, John V. ;

Johnson, Bruce E. ;

Cantley, Lewis C. ;

Janne, Pasi A. .

JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (10) :2695-2706

[10] The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism [J].

Engelman, Jeffrey A. ;

Luo, Ji ;

Cantley, Lewis C. .

NATURE REVIEWS GENETICS, 2006, 7 (08) :606-619

← 1 2 3 4 5 6 →