Marine-Derived Leads as Anticancer Candidates by Disrupting Hypoxic Signaling through Hypoxia-Inducible Factors Inhibition

• Published in: Marine drugs 2024-04, Vol.22 (4), p.143
• Main Authors: Garcia, Maria Rita, Andrade, Paula B, Lefranc, Florence, Gomes, Nelson G M
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Anticancer properties; Antimitotic agents; Antineoplastic agents; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antineoplastic drugs; Aquatic Organisms - chemistry; Basic Helix-Loop-Helix Transcription Factors - antagonists & inhibitors; Basic Helix-Loop-Helix Transcription Factors - metabolism; Biological Products - chemistry; Biological Products - pharmacology; Biological Products - therapeutic use; Cancer; Cancer therapies; caulerpin; Cell survival; Cellular signal transduction; Chemical properties; Chemotherapy; Cytotoxic agents; Cytotoxicity; discorhabdin; dolastatin-15; Drugs; echinomycin; epolactaene; fascaplysin; FDA approval; Gene expression; Health aspects; Humans; Hypoxia; Hypoxia-inducible factor 1; Hypoxia-Inducible Factor 1 - antagonists & inhibitors; Hypoxia-inducible factors; Inhibitors; Marine algae; Marine bacteria; Marine environment; Marine flora; Marine organisms; Metastases; Natural products; Neoplasms; Neoplasms - drug therapy; Neoplasms - pathology; Pharmaceutical research; Physiological aspects; Proteins; Radiation therapy; Signal Transduction - drug effects; Solid tumors; Templates; Transcription factors; Tumors; Vascularization
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md22040143

The inadequate vascularization seen in fast-growing solid tumors gives rise to hypoxic areas, fostering specific changes in gene expression that bolster tumor cell survival and metastasis, ultimately leading to unfavorable clinical prognoses across different cancer types. Hypoxia-inducible factors (HIF-1 and HIF-2) emerge as druggable pivotal players orchestrating tumor metastasis and angiogenesis, thus positioning them as prime targets for cancer treatment. A range of HIF inhibitors, notably natural compounds originating from marine organisms, exhibit encouraging anticancer properties, underscoring their significance as promising therapeutic options. Bioprospection of the marine environment is now a well-settled approach to the discovery and development of anticancer agents that might have their medicinal chemistry developed into clinical candidates. However, despite the massive increase in the number of marine natural products classified as 'anticancer leads,' most of which correspond to general cytotoxic agents, and only a few have been characterized regarding their molecular targets and mechanisms of action. The current review presents a critical analysis of inhibitors of HIF-1 and HIF-2 and hypoxia-selective compounds that have been sourced from marine organisms and that might act as new chemotherapeutic candidates or serve as templates for the development of structurally similar derivatives with improved anticancer efficacy.