The findings could potentially improve the success rate of cancer drug development. Approximately 90% of drugs don't reach the market, highlighting the clear need for increased efficiency in drug development. The story isn't different for drugs aimed at treating cancer, with many failing due to var
Fluorescent image showing cells with normal nucleoli in nuclei surrounded by actin filaments . Credit: Image courtesy of Tamara Potapova, Gerton Lab, Stowers Institute for Medical ResearchApproximately 90% of drugs don’t reach the market, highlighting the clear need for increased efficiency in drug development. The story isn’t different for drugs aimed at treating cancer, with many failing due to various reasons.
Graphical illustration of a normal nucleolus and its extreme stress state following transcriptional cyclin-dependent kinase inhibition by chemotherapy agents. Credit: Image courtesy of Mark Miller and Tamara Potapova, Stowers Institute for Medical Research, and where ribosomalproduction and ribosome assembly largely takes place. Nucleoli can vary greatly in appearance, serving as visual indicators of the overall health of this process.
Different drugs impact different pathways involved in cancer growth. Those that influence ribosome production can induce distinct states of nucleolar stress that manifest in easily seen morphological changes. However, nucleolar stress can be difficult to measure. Through the comprehensive screening of anti-cancer compounds on nucleolar stress, the team identified one class of enzymes in particular, cyclin-dependent kinases, whose inhibition destroys the nucleolus almost completely. Many of these inhibitors failed in clinical trials, and their detrimental impact on the nucleolus was not fully appreciated previously.
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