Protein kinase C inhibitors |
| |
Authors: | Helen C Swannie Stanley B Kaye |
| |
Institution: | (1) CRC Department of Medical Oncology, Royal Marsden Hospital, SM2 5NG Sutton, Surrey, UK |
| |
Abstract: | Protein kinase C (PKC) is a family of serine-threonine protein kinases that are involved in signal transduction pathways that
regulate growth factor response, proliferation, and apoptosis. Its central role in these processes, which are closely involved
in tumor initiation, progression, and response to antitumor agents, makes it an attractive therapeutic target in cancer. Despite
initial activity seen in melanoma (bryostatin and UCN-01), non-Hodgkin’s lymphoma (ISIS 3521, bryostatin, and UCN-01), and
ovarian carcinoma (ISIS 3521 and bryostatin) in phase I studies, single-agent activity in those phase II studies reported
to date has been limited. Preclinical data highlight a role for PKC in modulation of drug resistance and synergy with conventional
cytotoxic drugs. A randomized phase III study of ISIS 3521 in combination with carboplatin and paclitaxel, compared with chemotherapy
alone, in advanced non-small-cell lung cancer is underway. This paper reviews the rationale for using PKC inhibitors in cancer
therapy, the challenges for clinical trial design, and the recent clinical experience with modulators of PKC activity. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|