Cited by 185Protein Kinase Regulation and GTPase SignalingPI3K/AKT/mTOR signaling in cancerSignaling Pathways in Disease

Bryostatin-1: A novel PKC inhibitor in clinical development

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

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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Crossref · 10.1081/cnv-120025095

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108 of 108 references verified0 citation errors · 0 not checkable

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  • Bryostatin modulates the paclitaxel inhibitor of protein kinase C (PKC).

    “Another chemotherapeutic agent is bryostatin that modulates the paclitaxel inhibitor of protein kinase C (PKC) [224].”

    From Marine Natural Products: A Source of Novel Anticancer Drugs (2019) · cites this paper as [224]

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Authors
Kortmansky, J., & Schwartz, G. K.
Affiliations
Memorial Sloan Kettering Cancer Center (US)
Venue
Cancer Investigation
Published
2003-01
Volume
21
Issue
6
Pages
924-936
ISSN
  • 0735-7907 (ISSN-L)
  • 1532-4192
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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