INHIBITORS OF PHOSPHATIDYLINOSITOL SIGNALING AS ANTIPROLIFERATIVE AGENTS

被引:29
作者
POWIS, G
机构
[1] Arizona Cancer Center, University of Arizona Health Sciences Center, Tucson, 85724, AZ
关键词
PHOSPHATIDYLINOSITOL; INTRACELLULAR SIGNALING; PHOSPHOLIPASE-C; PHOSPHATIDYLINOSITOL-3-KINASE; CANCER;
D O I
10.1007/BF00690420
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Intracellular signalling pathways mediating the effects of oncogenes on cell growth and transformation offer novel targets for the development of anticancer drugs. With this approach it may be sufficient to target a component of the signalling pathway activated by the oncogene rather than the oncogene product itself. Phosphatidylinositol (PtdIns) is a key component of two growth factor signalling pathways. It acts as a substrate for PtdIns specific phospholipase C (PtdInsPLC) and for PtdIns-3-kinase. In this review the antiproliferative properties of some inhibitors of PtdInsPLC and PtdIns-3-kinase are considered. There are some compounds already in clinical trial as anticancer drugs that may act by inhibiting PtdIns signalling, as well as several compounds in preclinical development. Some problems that may be encountered in developing this new class of anticancer drugs are discussed.
引用
收藏
页码:91 / 103
页数:13
相关论文
共 93 条
  • [1] TRANSFORMING RAS GENES FROM HUMAN-MELANOMA - A MANIFESTATION OF TUMOR HETEROGENEITY
    ALBINO, AP
    LESTRANGE, R
    OLIFF, AI
    FURTH, ME
    OLD, LJ
    [J]. NATURE, 1984, 308 (5954) : 69 - 72
  • [2] ALINEC G, 1992, MOL CELL BIOL, V12, P4687
  • [3] Andreesen R, 1988, Prog Biochem Pharmacol, V22, P118
  • [4] STRUCTURE OF A NOVEL PHOSPHOLIPASE-C INHIBITOR, VINAXANTHONE (RO-09-1450), PRODUCED BY PENICILLIUM-VINACEUM
    AOKI, M
    ITEZONO, Y
    SHIRAI, H
    NAKAYAMA, N
    SAKAI, A
    TANAKA, Y
    YAMAGUCHI, A
    SHIMMA, N
    YOKOSE, K
    SETO, H
    [J]. TETRAHEDRON LETTERS, 1991, 32 (36) : 4737 - 4740
  • [5] ELEVATED CONTENT OF THE TYROSINE KINASE SUBSTRATE PHOSPHOLIPASE C-GAMMA-1 IN PRIMARY HUMAN BREAST CARCINOMAS
    ARTEAGA, CL
    JOHNSON, MD
    TODDERUD, G
    COFFEY, RJ
    CARPENTER, G
    PAGE, DL
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (23) : 10435 - 10439
  • [6] BERGGREN MI, 1993, CANCER RES, V53, P4297
  • [7] INOSITOL PHOSPHATES AND CELL SIGNALING
    BERRIDGE, MJ
    IRVINE, RF
    [J]. NATURE, 1989, 341 (6239) : 197 - 205
  • [8] INOSITOL LIPIDS AND CELL-PROLIFERATION
    BERRIDGE, MJ
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1987, 907 (01) : 33 - 45
  • [9] BISHAYEE S, 1989, J BIOL CHEM, V264, P11699
  • [10] BLEASDALE JE, 1989, ADV PROSTAG THROMB L, V19, P590