BH3 mimetics as a strategy to complement anticancer therapies
Journal Title: Advances in Hygiene and Experimental Medicine - Year 2012, Vol 66, Issue 0
Abstract
The basis for targeting specific components of the apoptotic machinery for anticancer therapy is the detailed knowledge on molecular mechanisms that regulate this complex cell death pathway. As the mitochondrial pathway of apoptosis is the major route to respond to stress stimuli including anticancer drugs, and that pathway is largely impaired in cancer cells, leading to tumor formation and treatment resistance, a variety of approaches have been developed to restore the function of the mitochondrial pathway in cancer cells. BH3-only proteins, being important inducers of the mitochondrial pathway, either directly stimulate proapoptotic Bax-like proteins or interfere with antiapoptotic Bcl-2 proteins. Therefore, the development of molecules able to mimic the function of BH3-only proteins is considered a promising strategy to improve cancer cell response to treatment. Several BH3 mimetics have been designed and studied in various tumors, in both in vitro and in vivo settings. Some of them are currently being evaluated in clinical trials either alone or in combination with conventional anticancer drugs. BH3 profiling of cancer cells was introduced to better predict the responsiveness of tumor cells to BH3 mimetics combined with conventional therapies. In this review, we summarize the current knowledge on BH3-only proteins and describe the spectrum of strategies employing BH3 mimetics in preclinical and clinical studies that aim at tumor targeting.
Authors and Affiliations
Mariusz Hartman, Małgorzata Czyż
Keywords
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