The clinical development of the bryostatins

被引:81
作者
Clamp, A [1 ]
Jayson, GC [1 ]
机构
[1] Christie Hosp NHS Trust, Dept Med Oncol, Canc Res UK, Manchester M20 4BX, Lancs, England
关键词
bryostatin; protein kinase C; signal transduction;
D O I
10.1097/00001813-200208000-00001
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The bryostatins are a group of novel macrocyclic lactones derived from the marine bryozoan, Bugula neritina. In vitro evidence indicates that their main mechanism of action is modulation of protein kinase C (PKC) activity. Phase I studies suggested significant antineoplastic activity against several tumor types and defined the main dose-limiting toxicity as myalgla. Bryostatin-1 has subsequently been investigated extensively in phase II clinical trials as a single agent, although trial design has been hampered by lack of human pharmacokinetic data. Results have been generally disappointing but in vitro and animal data suggests an important role for bryostatin-1 in combination with cytotoxic agents. Preliminary results of phase I studies support these observations but further work needs to be done to define the future role of the bryostatins in the clinic. [(C) 2002 Lippincott Williams Wilkins.].
引用
收藏
页码:673 / 683
页数:11
相关论文
共 84 条
  • [41] The catalytic domain of protein kinase Cδ confers protection from down-regulation induced by bryostatin 1
    Lorenzo, PS
    Bögi, K
    Acs, P
    Pettit, GR
    Blumberg, PM
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (52) : 33338 - 33343
  • [42] Bryostatin 1 induces biphasic activation of protein kinase D in intact cells
    Matthews, SA
    Pettit, GR
    Rozengurt, E
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (32) : 20245 - 20250
  • [43] MAY WS, 1993, BLOOD, V82, pA438
  • [44] ANTINEOPLASTIC BRYOSTATINS ARE MULTIPOTENTIAL STIMULATORS OF HUMAN HEMATOPOIETIC PROGENITOR CELLS
    MAY, WS
    SHARKIS, SJ
    ESA, AH
    GEBBIA, V
    KRAFT, AS
    PETTIT, GR
    SENSENBRENNER, LL
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (23) : 8483 - 8487
  • [45] MCCRADY CW, 1993, EXP HEMATOL, V21, P893
  • [46] Merchant RE, 1997, NEUROL RES, V19, P145
  • [47] MOHAMMAD RM, 1994, CANCER RES, V54, P165
  • [48] Potentiation of 2-chlorodeoxyadenosine activity by bryostatin 1 in the resistant chronic lymphocytic leukemia cell line (WSU-CLL):: Association with increased ratios of dCK/5′-NT and Bax/Bcl-2
    Mohammad, RM
    Beck, FWJ
    Katato, K
    Hamdy, N
    Wall, N
    Al-Katib, A
    [J]. BIOLOGICAL CHEMISTRY, 1998, 379 (10) : 1253 - 1261
  • [49] Mohammad RM, 1998, CLIN CANCER RES, V4, P445
  • [50] Mohammad RM, 2000, CLIN CANCER RES, V6, P4950