Simon Lab at the FHCRC
Yeast Screen of Anticancer Agents
These data have not been endorsed by the National Cancer Institute or the Fred Hutchinson Cancer Research Center.
The examination of the differential sensitivities of the DNA damage response-deficient yeast strains to anticancer agents was driven by the hypothesis that some of the changes that lead to genetic instability often associated with human cancers can be exploited therapeutically. The yeast panel is composed of strains that are deficient for specific DNA repair and cell cycle checkpoint functions. In many cases the yeast gene (e.g MLH1) has a human homologue and in both organisms the loss of this gene leads to a similar type of genetic instability (e.g. microsatellite instability). Where possible, we have included multiple yeast strains that correspond to loss of function in a specific pathway. This allows us to determine whether the sensitivity of a particular strain is due that specific mutation or to a general pathway defect.
We chose to examine the non-biological, non-hormonal FDA-approved anticancer agents to determine whether these drugs work because they target specific damage response functions. We were able to obtain profiles on 23 of the 44 agents that are expected to be active in yeast. These represent all major classes of cytotoxic anticancer agents except the spindle poisons.
This work was supported by the Developmental Therapeutic Program of the National Cancer Institute.
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