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.
Reviewed by Lily Ramsey, LLMAug 23 2023 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.
Tamara Potapova, Ph.D., lead author, research specialist in the lab of Investigator Jennifer Gerton, Ph.D. Because cancer's hallmark is unchecked proliferation, most existing chemotherapeutic agents are designed to slow this down. "The logic was to see whether these drugs, intentionally or unintentionally, are affecting ribosome biogenesis and to what degree," said Potapova. "Hitting ribosome biogenesis could be a double-edged sword-;it would impair the viability of cancer cells while simultaneously altering protein production in normal cells.
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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