Opinion - Searching for the elusive targets of farnesyltransferase inhibitors

被引：143

作者：

Sebti, SM

Der, CJ ^{[1
]}

机构：

[1] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA

[2] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Oncol,Drug Discovery Program, Tampa, FL 33612 USA

来源：

NATURE REVIEWS CANCER | 2003年 / 3卷 / 12期

关键词：

D O I：

10.1038/nrc1234

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Farnesyltransferase (FTase) inhibitors (FTIs) were developed originally as anti-RAS compounds and novel target-based drugs for cancer treatment. The analyses of FTIs continue in the clinic, but the antitumour activity cannot be ascribed simply to inhibition of RAS. Although FTI action is due to inhibition of FTase, and RAS proteins are indeed substrates for this enzyme, the RAS proteins that are most frequently mutated in human cancers escape FTI inhibition. RHOB has been suggested as a target, but is this issue resolved or do the crucial targets of FTIs remain to be identified?

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页码：945 / 951

页数：7

相关论文

共 82 条

[1]

Adnane J, 2002, CLIN CANCER RES, V8, P2225

[2] RhoA prenylation is required for promotion of cell growth and transformation and cytoskeleton organization but not for induction of serum response element transcription [J].

Allal, C ;

Favre, G ;

Couderc, B ;

Salicio, S ;

Sixou, S ;

Hamilton, AD ;

Sebti, SM ;

Lajoie-Mazenc, I ;

Pradines, A .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (40) :31001-31008

[3]

Alton G, 2001, METHOD ENZYMOL, V332, P300

[4] CAAX GERANYLGERANYL TRANSFERASE TRANSFERS FARNESYL AS EFFICIENTLY AS GERANYLGERANYL TO RHOB [J].

ARMSTRONG, SA ;

HANNAH, VC ;

GOLDSTEIN, JL ;

BROWN, MS .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (14) :7864-7868

[5] Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules [J].

Ashar, HR ;

James, L ;

Gray, K ;

Carr, D ;

Black, S ;

Armstrong, L ;

Bishop, WR ;

Kirschmeier, P .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (39) :30451-30457

[6] RAS GENES [J].

BARBACID, M .

ANNUAL REVIEW OF BIOCHEMISTRY, 1987, 56 :779-827

[7] RhoB prenylation is driven by the three carboxyl-terminal amino acids of the protein:: Evidenced in vivo by an anti-farnesyl cysteine antibody [J].

Baron, R ;

Fourcade, E ;

Lajoie-Mazenc, I ;

Allal, C ;

Couderc, B ;

Barbaras, R ;

Favre, G ;

Faye, JC ;

Pradines, A .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (21) :11626-11631

[8] Inhibition of Ras and related G-proteins as a therapeutic strategy for blocking malignant glioma growth [J].

Bredel, M ;

Pollack, IF ;

Freund, JM ;

Hamilton, AD ;

Sebti, SM .

NEUROSURGERY, 1998, 43 (01) :124-131

[9] Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner [J].

Castro, AF ;

Rebhun, JF ;

Clark, GJ ;

Quilliam, LA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (35) :32493-32496

[10] Prenylation of oncogenic human PTPCAAX protein tyrosine phosphatases [J].

Cates, CA ;

Michael, RL ;

Stayrook, KR ;

Harvey, KA ;

Burke, YD ;

Randall, SK ;

Crowell, PL ;

Crowell, DN .

CANCER LETTERS, 1996, 110 (1-2) :49-55

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