According to Prives, “The data raises the possibility that we might identify subsets of patients whose tumors may respond to statins. There are great implications, but nothing clinical yet. Perhaps one could do a clinical trial, and that may support these findings, or it may be more complicated.” The study is being published in the journal Cell.
P53 is a tumor suppressor gene known to help control many aspects of cell growth, such as keeping it organized and blocking uncontrolled growth. Over 50% of us have a mutated form of p53, most of these mutations don’t just disrupt the gene’s normal job, they also give it the ability to promote, instead of suppress, the development of cancer.
Experiments in mice have demonstrated that when they lack p53 they develop cancer and die. However, when they carry forms of p53 taken from tumors, they develop a more aggressive cancer. However, what the mutant forms of p53 are actually doing remains unclear and is still a big question mark for cancer researchers.
To investigate mutant forms of p53 further, the researchers studied cancer cells growing in an artificial system that replicates the three-dimensional structure of the human breast. There they observed cells with mutant p53 genes growing in a chaotic and invasive manner, exactly like breast cancer in the human body. However, when they lowered the amount of cells carrying mutant p53, the cells grew more normally in their 3d structure.
The next phase of the study involved author William Freed-Pastor from Columbia University. He and his fellow researchers found that a pathway known as the mevalonate pathway was responsible for the structural changes in the disorganized growth of the mutated p53-carrying cells. This pathway is the same one targeted by cholesterol-lowering statins because it also makes cholesterol.
This sparked the interest of researchers who wanted to see what happens if you treat the cells with statins. When they did this, the researchers found that the mutant p53 cells stopped their disorganized, invasive growth, and some of them even died.
Finally, with colleagues from the University of Oslo in Norway, Freed-Pastor and Prives examined breast cancer tissue taken from tumors in human patients and discovered that mutations in p53 and an increased rate of activity in the mevalonate pathway tend to coincide in humans as well. They note that it correlates with the highly expressed sterol biosynthesis genes in human breast tumors.
The authors conclude that these findings implicate the mevalonate as a therapeutic target for tumros bearing mutations in p53. However, while these findings are encouraging, much more research is required before they can be applied in a clinical setting.