Pharmacology and clinical experience with bryostatin 1: a novel anticancer drug

Abstract

Bryostatin 1 (bryo 1) is an example of a novel class of anticancer drug which modulates protein kinase C (PKC) activity. It has varied biological effects mediated largely by the initial activation of PKC, followed by its rapid downregulation. Bryo 1 stimulates in vitro and in vivo haematopoietic progenitor cell growth in a concentration-dependent and lineage-specific fashion. Granulocytes, lymphocytes, monocytes and platelets are all functionally stimulated by bryo 1. Stimulation of cytotoxic T-cell activity by bryo 1 has led to research utilising bryo 1 as an immunotherapeutic agent in mouse tumour xenograft models. The clinical development of bryo 1 followed the demonstration of direct in vitro activity against various tumour cell lines. Multiple Phase I trials have shown muscle pain and flu-like symptoms are the most common toxicities associated with administration of bryo 1. There is particular interest in the role of bryo 1 in haematologic malignancies because of its capacity to induce leukaemic cell differentiation. There is ample in vitro data demonstrating that bryo 1 can sensitise tumour cells to cytotoxic agents. Recent clinical work has focused on combining bryo 1 with traditional chemotherapeutic agents for both haematologic and non-haematologic cancers.

• bryostatin 1
• drug resistance
• protein kinase C
• PKC
• phorbol esters