New Insights into Cellular Processes Behind Drug-Resistant Cancers

Scientists are uncovering critical cellular mechanisms that enable cancers to develop resistance against treatments, a major challenge in oncology. Recent research from the University of Ottawa has shed light on how cancer cells bypass cell cycle checkpoints that would normally halt their division when DNA is damaged, allowing them to multiply uncontrollably. The study, published in the Proceedings of the National Academy of Sciences, highlights the role of centrosomes—small organelles within cells—in facilitating this process. It was found that centrosomes act as signaling hubs, promoting cell proliferation even in the presence of unrepaired DNA damage.

Specifically, the research demonstrated that the enzyme Polo-like kinase 1 (PLK1) is recruited to centrosomes during these events, encouraging cells to divide despite damage. This process can contribute to the rapid accumulation of mutations, mirroring the behavior of treatment-resistant tumors. Dr. Damien D'Amours, a Canada Research Chair in Chromatin Dynamics, notes that understanding this pathway offers promising avenues for therapeutic intervention, especially since many chemotherapy agents target DNA damage.

The team used a systems biology approach, examining model organisms such as yeast, to understand how centrosomes and PLK1 interact to influence adaptation to DNA damage. Their findings reveal that inhibiting PLK1 could be a potential strategy to prevent cancer cells from proliferating in the face of DNA-damaging treatments. Moving forward, the researchers aim to validate these findings clinically to enhance the efficacy of radio- and chemotherapy by blocking this resistance mechanism.

This breakthrough enhances our understanding of how cancer cells evade treatment and opens new pathways for developing targeted therapies that disrupt these cellular adaptations, ultimately aiming to improve patient outcomes in resistant cancers.