Development of TGF-β signalling inhibitors for cancer therapy

被引：466

作者：

Yingling, JM ^{[1
]}

Blanchard, KL ^{[1
]}

Sawyer, JS ^{[1
]}

机构：

[1] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA

来源：

NATURE REVIEWS DRUG DISCOVERY | 2004年 / 3卷 / 12期

关键词：

D O I：

10.1038/nrd1580

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The transforming growth factor-beta (TGF-beta) superfamily of ligands has a pivotal role in the regulation of a wide variety of physiological processes from development to pathogenesis. Since the discovery of the prototypic member, TGF-beta, almost 20 years ago, there have been tremendous advances in our understanding of the complex biology of this superfamily. Deregulation of TGF-beta has been implicated in the pathogenesis of a variety of diseases, including cancer and fibrosis. Here we present the rationale for evaluating TGF-beta signalling inhibitors as cancer therapeutics, the structures of small-molecule inhibitors that are in development and the targeted drug discovery model that is being applied to their development.

引用

页码：1011 / 1022

页数：12

共 119 条

[61] Cyclin-dependent kinases regulate the antiproliferative function of Smads [J].

Matsuura, I ;

Denissova, NG ;

Wang, GN ;

He, DM ;

Long, JY ;

Liu, F .

NATURE, 2004, 430 (6996) :226-231

[62] Evaluation of anti-TGF-β2 antibody as a new postoperative anti-scarring agent in glaucoma surgery [J].

Mead, AL ;

Wong, TTL ;

Cordeiro, MF ;

Anderson, IK ;

Khaw, PT .

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2003, 44 (08) :3394-3401

[63] Lerdelimumab.: Prevention of corneal scarring. [J].

Mealy, NE ;

Bayés, M .

DRUGS OF THE FUTURE, 2003, 28 (04) :320-322

[64]

Mendel DB, 2003, CLIN CANCER RES, V9, P327

[65] Gene expression profiling of human colon xenograft tumors following treatment with SU11248, a multitargeted tyrosine kinase inhibitor [J].

Morimoto, AM ;

Tan, N ;

West, K ;

McArthur, G ;

Toner, GC ;

Manning, WC ;

Smolich, BD ;

Cherrington, JM .

ONCOGENE, 2004, 23 (08) :1618-1626

[66]

MUNCHHOF MJ, 2004, Patent No. 2004147574

[67] Increased malignancy of neu-induced mammary tumors overexpressing active transforming growth factor β1 [J].

Muraoka, RS ;

Koh, Y ;

Roebuck, LR ;

Sanders, ME ;

Brantley-Sieders, D ;

Gorska, AE ;

Moses, HL ;

Arteaga, CL .

MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (23) :8691-8703

[68] Blockade of TGF-β inhibits mammary tumor cell viability, migration, and metastases [J].

Muraoka, RS ;

Dumont, N ;

Ritter, CA ;

Dugger, TC ;

Brantley, DM ;

Chen, J ;

Easterly, E ;

Roebuck, LR ;

Ryan, S ;

Gotwals, PJ ;

Koteliansky, V ;

Arteaga, CL .

JOURNAL OF CLINICAL INVESTIGATION, 2002, 109 (12) :1551-1559

[69] Metastasis is driven by sequential elevation of H-ras and Smad2 levels [J].

Oft, M ;

Akhurst, RJ ;

Balmain, A .

NATURE CELL BIOLOGY, 2002, 4 (07) :487-494

[70] EGFR mutations in lung cancer:: Correlation with clinical response to gefitinib therapy [J].

Paez, JG ;

Jänne, PA ;

Lee, JC ;

Tracy, S ;

Greulich, H ;

Gabriel, S ;

Herman, P ;

Kaye, FJ ;

Lindeman, N ;

Boggon, TJ ;

Naoki, K ;

Sasaki, H ;

Fujii, Y ;

Eck, MJ ;

Sellers, WR ;

Johnson, BE ;

Meyerson, M .

SCIENCE, 2004, 304 (5676) :1497-1500

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