Researchers from Johns Hopkins Medicine have revealed a crucial molecular pathway that drives cells toward uncontrolled genome duplication
This discovery shows the mechanisms underlying cancer development and offers promising routes for targeted therapies.
“An enduring question among scientists in the cancer field is: How do cancer cell genomes get so bad?” says Sergi Regot
The progression of the cell cycle
The study, led by Dr Sergi Regot and graduate research assistant Connor McKenney, focused on understanding how cells navigate the process of the cell cycle, where they replicate their genetic material and divide to form new cells.
By observing human breast and lung cells, which show rapid division rates, the researchers were able to capture the subtle nuances of this complex biological process.
The cell cycle during stress
One of the key findings of the study was the identification of a series of molecules and enzymes that regulate the cell cycle, particularly during times of environmental stress.
When cells experience stressors like UV radiation or changes in water pressure, a group of enzymes called cyclin-dependent kinases (CDKs) become dysregulated, disrupting the normal progression of the cell cycle.
The researchers observed that a small percentage of cells, approximately 5% to 10%, were resistant to entering a dormant state in response to stress. Instead, these cells continued to replicate their genome.
Further investigation revealed that the activation of stress-activated protein kinases played a critical role in driving these resistant cells to avoid the dormant stage and undergo repeated genome duplication. This behaviour eventually contributes to the formation of cancerous tumours.
Targeting cancer cells
The study also identified potential therapeutic targets for disrupting this harmful pathway. Drugs that inhibit CDK activity or block the activation of a protein complex called the anaphase promoting complex (APC) show promise in preventing cancer cells from undergoing excessive genome duplication.
Dr. Regot emphasised the significance of these findings in the context of cancer treatment. He pointed out that ongoing clinical trials are exploring the efficacy of combination therapies involving DNA-damaging agents and CDK inhibitors.
By understanding the molecular mechanisms driving cancer cell growth, researchers hope to develop more effective treatments that can overcome drug resistance and improve patient outcomes.
