Bryostatin-1: A novel PKC inhibitor in clinical development Journal Article

  


Authors: Kortmansky, J.; Schwartz, G. K.
Article Title: Bryostatin-1: A novel PKC inhibitor in clinical development
Abstract: Modulation of PKC represents a novel approach to cancer therapy. Bryostatin-1 is a macrocyclic lactone derived from a marine invertebrate that binds to the regulatory domain of protein kinase C. Short-term exposure to bryostatin-1 promotes activation of PKC, whereas prolonged exposure promotes significant downregulation of PKC. In numerous hematological and solid tumor cell lines, bryostatin-1 inhibits proliferation, induces differentiation, and promotes apoptosis. Furthermore, preclinical studies indicate that bryostatin-1 potently enhances the effect of chemotherapy. In many cases, this effect is sequence specific. Bryostatin-1 is currently in phase I and phase II clinical trials. The major toxicities are myalgias, nausea, and vomiting. Although there is minimal single-agent activity, combinations with standard chemotherapy are providing very encouraging results and indicate a new direction in cancer therapy.
Keywords: clinical trial; constipation; fatigue; neutropenia; review; cisplatin; cancer combination chemotherapy; diarrhea; side effect; solid tumor; antineoplastic agents; paclitaxel; cell proliferation; apoptosis; liver toxicity; pain; bleeding; leukopenia; nausea; thrombocytopenia; vomiting; myalgia; down-regulation; vincristine; bradycardia; cell differentiation; antineoplastic activity; drug potency; drug effect; drug screening; drug hypersensitivity; dyspnea; fever; flushing; rash; chemotherapy induced emesis; hypotension; hematologic malignancy; drug mechanism; tumor cell line; protein kinase c; down regulation; headache; drug blood level; bryostatin 1; photophobia; supraventricular tachycardia; drug exposure; macrocyclic compound; cellulitis; protein kinase c inhibitor; eye pain; lactone derivative; lactones; macrolides; clinical trials, phase ii; clinical trials, phase i; invertebrate; humans; human; priority journal
Journal Title: Cancer Investigation
Volume: 21
Issue: 6
ISSN: 0735-7907
Publisher: Informa Healthcare  
Date Published: 2003-01-01
Start Page: 924
End Page: 936
Language: English
DOI: 10.1081/cnv-120025095
PUBMED: 14735696
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-0346096818&partnerID=40&md5=63ba46e2dc4615cd59f08c0d537d5922
Notes: Export Date: 25 September 2014 -- Source: Scopus
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MSK Authors
  1. Gary Schwartz
    385 Schwartz
  2. Jeremy Kortmansky
    17 Kortmansky
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