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Bryostatin-1: A Novel PKC Inhibitor in Clinical Development

Kortmansky, Jeremy, Schwartz, Gary K.·2003·Cancer Investigation

DOI 10.1081/cnv-120025095

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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.

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Authors: Kortmansky, J., & Schwartz, G. K.
Affiliations: Memorial Sloan Kettering Cancer Center (US)
ORCID: Kortmansky, Jeremy
Schwartz, Gary K.
Venue: Cancer Investigation
Publisher: Informa UK Limited
Published: 2003-01
Volume: 21
Issue: 6
Pages: 924-936
ISSN: 0735-7907 (ISSN-L)
1532-4192
DOI: 10.1081/cnv-120025095
OpenAlex: W1996339149
Cited by: 183
References: 109
Citations by year: 2026: 5 · 2025: 10 · 2024: 5 · 2023: 2 · 2022: 8 · 2021: 7 · 2020: 8 · 2019: 6 · 2018: 3 · 2017: 12 · 2016: 9 · 2015: 7 · 2014: 13 · 2013: 4 · 2012: 12
FWCI: 2.07
Type: journal article
Language: en
Open access: closed
Locations: Cancer Investigation (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (R01CA67819, CA09207, R01CA067819, T32CA009207)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords: bryostatin 1, protein kinase C, PKC inhibitors, macrocyclic lactones, marine natural products, cancer therapy, chemosensitization, apoptosis, cell differentiation, hematologic malignancies, solid tumors, drug toxicity, clinical trials
MeSH terms: Antineoplastic Agents, Cell Differentiation, Humans, Lactones, Nausea, Pain, Protein Kinase C, Vomiting, Down-Regulation, Apoptosis, Clinical Trials, Phase I as Topic, Clinical Trials, Phase II as Topic, Macrolides, Bryostatins

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Bryostatin-1: A Novel PKC Inhibitor in Clinical Development

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