Preclinical and clinical evaluation of farnesyltransferase inhibitors

被引：23

作者：

Charles Baum

Paul Kirschmeier

机构：

[1] Schering-Plough Research Institute, Kenilworth, NJ 07033-1300

来源：

Current Oncology Reports | 2003年 / 5卷 / 2期

关键词：

Paclitaxel; Gemcitabine; Chronic Myeloid Leukemia; Maximum Tolerate Dose; Advanced Solid Tumor;

D O I：

10.1007/s11912-003-0096-5

中图分类号：

学科分类号：

摘要：

Farnesylation of Ras, a protooncogene that is frequently mutated in a number of malignancies, is critical for its biologic function. This observation has led to the development of several agents that inhibit farnesyltransferase, known as farnesyltransferase inhibitors (FTIs). The antiproliferative and antitumor effects of these agents have been demonstrated in preclinical and clinical studies. Interestingly, FTI activity does not necessarily rely on ras mutational status, indicating, that Ras is not the only FTI target. Clinical data suggest that FTIs, alone and in combination with other agents, have antitumor activity. Further study is needed to determine the precise mechanism of FTI antitumor activity as well as how and where FTIs will be best used clinically. Copyright © 2003 by Current Science Inc.

引用

页码：99 / 107

页数：8

共 84 条

[1]

Rowinsky E.K., Windle J.J., Von Hoff D.D., Ras protein farnesyltransferase: A strategic target for anticancer therapeutic development, J. Clin. Oncol., 17, pp. 3631-3652, (1999)

[2]

Stokoe D., Macdonald S.G., Cadwallader K., Et al., Activation of Raf as a result of recruitment to the plasma membrane, Science, 264, pp. 1463-1467, (1994)

[3]

Campbell S.L., Khosravi-Far R., Rossman K.L., Et al., Increasing complexity of Ras signaling, Oncogene, 17, pp. 1395-1413, (1998)

[4]

Keely P.J., Westwick J.K., Whitehead I.P., Et al., Cdc42 and Rac1 induce integrin-mediated cell motility and invasiveness through PI(3)K, Nature, 390, pp. 632-636, (1997)

[5]

Kennedy S.G., Wagner A.J., Conzen S.D., Et al., The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal, Genes Dev., 11, pp. 701-713, (1997)

[6]

Gille H., Downward J., Multiple ras effector pathways contribute to G(1) cell cycle progression, J. Biol. Chem., 274, pp. 22033-22040, (1999)

[7]

Keely P.J., Rusyn E.V., Cox A.D., Et al., R-Ras signals through specific integrin alpha cytoplasmic domains to promote migration and invasion of breast epithelial cells, J. Cell Biol., 145, pp. 1077-1088, (1999)

[8]

Adjei A.A., Blocking oncogenic Ras signaling for cancer therapy, J. Natl. Cancer Inst., 93, pp. 1062-1074, (2001)

[9]

Casey P.J., Solski P.A., Der C.J., Et al., p21ras is modified by a farnesyl isoprenoid, Proc. Natl. Acad. Sci. U. S. A., 86, pp. 8323-8327, (1989)

[10]

James G., Goldstein J.L., Brown M.S., Resistance of K-RasBV12 proteins to farnesyltransferase inhibitors in Rat1 cells, Proc. Natl. Acad. Sci. U. S. A., 93, pp. 4454-4458, (1996)

← 1 2 3 4 5 6 7 8 9 →