A breakthrough study from researchers at the University of Melbourne has uncovered a vital genetic mechanism that sheds light on how a vital cancer-suppressing gene prevents tumors from developing. This research will not only help identify certain patients who are at a higher risk of developing specific cancers, but also directs researchers on a new path toward targeted and safer treatments.
It has been known for several decades that the p53 gene, and the subsequent p53 protein it encodes, is a major protective factor in the development of cancer. Known as a tumor suppressor gene, mutations or dysregulation in p53 is found to be a causative factor in over half of all cancers. In some cancers it plays an even bigger role, with mutated p53 found in nearly 70 percent of colon and pancreatic cancers.
The p53 protein acts a little like a checkpoint guard in the process of cell division. Its job is to pause the process of cell division if it identifies DNA damage or mutation. When a mutation is too significant to repair, p53 can signal a process called apoptosis, triggering cell death before the mutations can replicate. If the p53 gene is not working properly then damaged cells can replicate, causing cancerous tissue to grow and multiply.
Now, in world-first research, a team of researchers has uncovered a group of genes that is crucial to p53 effectively functioning in its cancer-preventing role. This group of genes is implicated in a DNA repair process, with one gene in particular, MLH1, found to be absolutely critical to p53 working properly.
"It was amazing to find that the loss of the DNA repair gene MLH1 prevented p53 from functioning properly, causing the development of lymphoma," says Marco Herold, one of the lead researchers on the project. "And when MLH1 was put back into the equation, tumor development was significantly stalled."
This discovery offers a valuable insight into how p53 communicates with DNA repair genes in preventing the development of cancers. Ana Janic, another lead researcher on the study, suggests this research could initially help doctors prescribe more effective treatments for patients.
"For instance, if a patient has lymphoma with a mutation that disables the DNA repair mechanism, doctors will now know to avoid certain DNA-damaging treatments, like chemotherapy, that may only make the cancer more aggressive," Janic says.
The p53 pathway is a promising new area in cancer research and finding new ways to modulate that pathway could be key to developing broad and effective treatments in the future. Discovering the fundamental relationship between these DNA repair genes, such as MLH1, and the efficacy of p53, will play a significant role in directing new research forward.
The study was published in the journal Nature Medicine.
Source: University of Melbourne
