Researchers Uncover Cellular Mechanism Behind Drug-Resistant Cancers
Understanding how cancer cells develop resistance to treatment is a critical issue in modern medicine, particularly given that this resistance accounts for approximately 90% of cancer-related fatalities. A recent study from the University of Ottawa's Faculty of Medicine offers new insights into the cellular processes that enable some cancers to evade therapeutic interventions.
Published in the Proceedings of the National Academy of Sciences, researchers led by Dr. Damien D'Amours and graduate student Laurence Langlois-Lemay have identified a significant mechanism through which cells with damaged DNA can bypass critical checkpoints in the cell cycle, allowing for uncontrolled division despite the presence of damage.
This discovery has important implications for the development of therapies aimed at combatting drug-resistant tumors, as many existing cancer treatments are designed to target and induce DNA damage in cancer cells.
Dr. D'Amours, a Canada Research Chair in Chromatin Dynamics and Genome Architecture, emphasizes that the team's findings could lead to more effective strategies for treating cancers that have become resistant to conventional therapies. The study indicates that centrosomes, which are small organelles responsible for various crucial cellular functions, play an unexpected role in signaling whether a cell can continue to divide in the presence of irreparable DNA damage.
Furthermore, the research suggests that inhibiting Polo-like kinase 1 (PLK1)--an enzyme integral to cell cycle regulation--could be a promising tactic to prevent cancer cells from adapting to DNA damage inflicted by treatments. The study highlights that enhanced recruitment of PLK1 to centrosomes is a vital step in enabling cells to proliferate despite severe DNA damage, a process that can ultimately lead to the generation of treatment-resistant tumors.
The research journey began in 2017, when Dr. D'Amours joined the University of Ottawa to investigate molecular pathways related to genome integrity. Langlois-Lemay, initially a master's student, utilized a systems biology approach in yeast--an organism well-regarded in genetic studies--to model how cells adapt to DNA damage. This foundational work has culminated in the current study, which provides a deeper understanding of the cellular mechanisms that underpin cancer resistance.
Looking ahead, the research team plans to validate their findings in clinical settings, specifically exploring how chemical inhibition of human PLK1 may reduce adaptation to DNA damage and enhance the efficacy of radio and chemotherapy treatments in cancer patients.
These advancements may pave the way for innovative therapeutic strategies that can more effectively target drug-resistant cancers, ultimately improving patient outcomes.