New Study Connects DNA Replication Defects with Cancer Treatment Strategies
New research from Karolinska Institutet uncovers how DNA replication regulation by CDK4/6 and RB proteins influences cancer development and treatment strategies, opening paths for targeted therapies.
A recent breakthrough from Karolinska Institutet, published in Nature Communications, sheds light on the pivotal role of cyclin-dependent kinases (CDKs), particularly CDK4/6, in the regulation of DNA replication in human cells. The study elucidates how these enzymes facilitate DNA replication licensing by mitigating inhibitory signals from the RB tumor suppressor proteins, a discovery that may significantly influence future cancer therapies.
Traditionally known as gatekeepers of the cell cycle, RB proteins have now been identified as key players in preparing the genome for duplication, a process called "replication licensing." This dual role of RB, modulated by phosphorylation through CDK4/6, not only commits cells to division but also ensures the genome is accurately copied, which explains the potent effectiveness of CDK4/6 inhibitors used in cancer treatment.
The researchers observed that combining these inhibitors with other agents that block DNA licensing led to abnormal cell division where cancer cells duplicated without proper DNA replication—a process particularly devastating to cells lacking the tumor suppressor gene p53, common in many cancers. This finding offers promising avenues for combination therapies that could selectively target cancer cells.
The biochemical studies involved advanced protein degradation techniques and high-sensitivity DNA sequencing, allowing unprecedented insight into DNA replication dynamics across the human genome. The research underscores the importance of RB in preventing replication stress and maintaining genomic stability, foundational in understanding how cancers develop and progress.
"Our discovery not only enhances our grasp of the cell cycle regulation but also opens new potential strategies for more effective, targeted cancer treatments," said senior author Dr. Bennie Lemmens. This research provides a new perspective on the complex regulation of DNA replication and highlights the potential of targeting these pathways in cancer therapies.
For further details, see the publication: DOI: 10.1038/s41467-025-63669-8. Source: https://medicalxpress.com/news/2025-09-links-dna-replication-failure-cancer.html
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