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Putting the brakes on tumorigenesis with snake venom toxins: New molecular insights for cancer drug discovery

Journal

SEMINARS IN CANCER BIOLOGY
Volume 80, Issue -, Pages 195-204

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcancer.2020.05.006

Keywords

Toxins; Cell death; Metastasis; Chemosensitization; Migrastatics

Categories

Funding

  1. FONDECYT [1180069]
  2. Programa de Investigacion Asociativa en Cancer Gastrico (PIA-CG) [RU2107]
  3. ANID PCI-Biotechnology [Redbio0027]

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Cancer cells have characteristics that allow them to adapt to stress conditions and promote their survival and proliferation. Current cytostatic drugs are ineffective against metastatic disease, highlighting the need for new therapeutic targets. Snake venom toxins have shown potential in suppressing cancer hallmarks, making them promising for anti-cancer drug development.
Cancer cells exhibit molecular characteristics that confer them different proliferative capacities and survival advantages to adapt to stress conditions, such as deregulation of cellular bioenergetics, genomic instability, ability to promote angiogenesis, invasion, cell dormancy, immune evasion, and cell death resistance. In addition to these hallmarks of cancer, the current cytostatic drugs target the proliferation of malignant cells, being ineffective in metastatic disease. These aspects highlight the need to identify promising therapeutic targets for new generations of anti-cancer drugs. Toxins isolated from snake venoms are a natural source of useful molecular scaffolds to obtain agents with a selective effect on cancer cells. In this article, we discuss the recent advances in the molecular mechanisms of nine classes of snake toxins that suppress the hallmarks of cancer by induction of oxidative phosphorylation dysfunction, reactive oxygen species-dependent DNA damage, blockage of extracellular matrix-integrin signaling, disruption of cytoskeleton network and inhibition of growth factor-dependent signaling. The possible therapeutic implications of toxin-based anti-cancer drug development are also highlighted.

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