Protein buildup may shape cancer drug response
The way cancer-causing proteins accumulate in tumors may influence how effectively a promising new generation of medicines can remove them, a study suggests. Researchers found that PROTAC (Proteolysis Targeting Chimeras) drugs were more effective at removing proteins that build up because they are not broken down properly than proteins that cancer cells continually produce in large amounts.
Researchers have discovered that how cancer-causing proteins accumulate in tumors can impact the effectiveness of new cancer-fighting drugs known as PROTACs. PROTACs, or Proteolysis Targeting Chimeras, are a novel class of medications that eliminate harmful proteins by utilizing the cell's natural waste disposal system. Unlike traditional drugs that merely inhibit the activity of disease-causing proteins, PROTACs aim to completely remove them.
The study, published in the journal Cell Chemical Biology, involved researchers from the University of Edinburgh who tested how PROTACs impact a protein called β-catenin, which plays a role in various cancers. They found that when β-catenin accumulated due to improper breakdown, the PROTACs were able to lower protein levels to a similar minimum, irrespective of the initial accumulation amount.
However, when β-catenin was produced at a higher rate, the protein levels persisted even after treatment because new protein continued to be synthesized.
This finding suggests that the success of PROTAC therapies may depend not only on the quantity of the cancer-driving protein present but also on the reason for its accumulation. According to Andrew Wood, the principal investigator at the University of Edinburgh's Institute of Genetics and Cancer, "By improving understanding of how tumor genetics shapes responses to targeted protein degradation, this study could help researchers identify which patients are most likely to benefit from these therapies and support the development of more personalized approaches to cancer treatment."
Professor Matthew Walters, chair of Medical Research Scotland, expressed support for the study, stating, "Medical Research Scotland is proud to have supported this important study, which we hope will help in the development of more targeted therapies for cancer. This research reflects our commitment to backing high-quality work with the potential to improve lives in Scotland and beyond."
The study highlights the importance of understanding the mechanisms behind the accumulation of oncogenic proteins, as this could influence the effectiveness of targeted protein degradation therapies.
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