Abstract
Despite the breakthroughs that have been achieved, significant unmet needs relating to the inadequate efficacy and toxicity of currently-available cancer therapies remain. Kinase inhibitors are a class of agents that target signaling factors responsible for the survival of malignant cells, and may address at least some of these issues. The concept of synthetic lethality provides a potential solution to counteract pathway redundancies, and refers to situations in which a mutation in one of two particular genes alone permits cell survival, while simultaneous mutation in both results in cell death. When exploited in the context of cancer therapy, pathways that are uniquely upregulated in cancer cells become selective targets, with reduced off-target toxicity toward their healthy counterparts. Natural compounds represent a large and readily-accessible library of bioactive structures that can be screened for synthetically lethal interactions by testing for the inhibition of kinases relevant to cancer cell survival. In this review, we discuss the concept of synthetic lethality and focus on scenarios in which natural compounds that target kinases may be applied to tip the balance in favor of cancer cell death during therapeutic challenge.
Keywords: Synthetic lethality, cancer, natural compounds, kinase, cancer therapy, selective killing, food compounds.
Current Pharmaceutical Design
Title:Induction of Synthetic Lethality by Natural Compounds Targeting Cancer Signaling
Volume: 23 Issue: 29
Author(s): Lee Farrand and Sanguine Byun*
Affiliation:
- Incheon National University, Building 29, 119 Academy-ro, Yeonsu-gu, Incheon 22012,Korea
Keywords: Synthetic lethality, cancer, natural compounds, kinase, cancer therapy, selective killing, food compounds.
Abstract: Despite the breakthroughs that have been achieved, significant unmet needs relating to the inadequate efficacy and toxicity of currently-available cancer therapies remain. Kinase inhibitors are a class of agents that target signaling factors responsible for the survival of malignant cells, and may address at least some of these issues. The concept of synthetic lethality provides a potential solution to counteract pathway redundancies, and refers to situations in which a mutation in one of two particular genes alone permits cell survival, while simultaneous mutation in both results in cell death. When exploited in the context of cancer therapy, pathways that are uniquely upregulated in cancer cells become selective targets, with reduced off-target toxicity toward their healthy counterparts. Natural compounds represent a large and readily-accessible library of bioactive structures that can be screened for synthetically lethal interactions by testing for the inhibition of kinases relevant to cancer cell survival. In this review, we discuss the concept of synthetic lethality and focus on scenarios in which natural compounds that target kinases may be applied to tip the balance in favor of cancer cell death during therapeutic challenge.
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Cite this article as:
Farrand Lee and Byun Sanguine *, Induction of Synthetic Lethality by Natural Compounds Targeting Cancer Signaling, Current Pharmaceutical Design 2017; 23 (29) . https://dx.doi.org/10.2174/1381612823666170710144106
DOI https://dx.doi.org/10.2174/1381612823666170710144106 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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