With around 90% of drugs failing to make it to market, the potential for improving efficiency within the drug development industry is clear. Drugs designed to combat cancers suffer similar rates of failure for many reasons. Now, researchers have revealed one reason why certain anti-cancer compounds can cause unexpected side effects. This research could help guide an understanding of why some drugs show more promise than others, providing a new tool that can be used to identify those drugs and drug candidates.
from the Stowers Institute for Medical Research screened over 1,000 existing anti-cancer drugs to assess how they impact the structure and function of the nucleolus, the ubiquitous cellular organelle where ribosomes are made.
The nucleolus is a special part of the cell nucleus that houses ribosomal DNA, and where ribosomal RNA production and ribosome assembly largely takes place. Nucleoli can vary greatly in appearance, serving as visual indicators of the overall health of this process. Thus, the team found a way to capitalize on this variation and asked how chemotherapy drugs impact the nucleolus, causing nucleolar stress.
"In this study, we not only evaluated how anti-cancer drugs alter the appearance of nucleoli, but also identified categories of drugs that cause distinct nucleolar shapes," said Gerton."This enabled us to create a classification system for nucleoli based on their appearance that is a resource other researchers can use."
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.
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