Getting back to my roots this week with a story on some good ole cancer research. Or should I say, more advances in the fight against cancer. We are fighting a battle, and just like in any battle, you have to get to the source of the problem. Over half of all cancers share mutations in the p53 gene. p53, which I’ll explain a bit more shortly, has been called the “master watchman” and the “guardian of the genome” – thus mutations in this gene are a major source of cancer problems.
Researchers at the University of Michigan Comprehensive Cancer Center recently presented some exciting work at the 102nd Annual Meeting of the American Association of Cancer Research. This work has not been published yet, but was led by Dr. Shaomeng Wang, whose laboratory website can be found here. They are hard at work developing a chemical compound that will work to block tumor growth by fixing problems with p53.
The image above is a simple explanation of the p53 “network”. Several actions in the cell, shown in the top box, will stimulate p53 and call it into action. These include damage to your DNA or something going wrong in normal cell division – serious problems. p53′s job is then to turn on many many other genes in the cell. The diverse functions of these genes are summarized in the boxes in the bottom. Basically, p53 wants the cell to stop whatever it’s doing and fix the problem before it continues – OR – if it can’t be fixed, p53 turns on genes that will lead to the death of the cell. Better to lose one cell rather than have it growing and dividing out of control. Unchecked cell growth is exactly how we get cancer = p53′s normal activity is VERY important.
Many current cancer drugs do indeed work to stimulate p53 activity, which is a good plan. However, they do this by causing DNA damage or things like that to activate p53. That is a problem though, because it’s the source of all the horrible side effects of chemotherapeutics.
A protein in the diagram that I ignored until now is MDM-2. This protein serves to block normal p53 activity. What Dr. Wang’s lab is working on is a drug that inhibits the MDM-2 protein. When you inactivate it, you will stimulate p53 and should suppress tumor growth. This is a new route for activating p53 in cancer cells – one that should cause less side effects.
Indeed, when the research team treated mice with tumors with this MDM-2 inhibitor, the tumors not only stopped growing, but shrunk over time. Additionally, the mice do not appear to exhibit any significant side effects, as the scientists would have expected. AND because this is such a problem across many cancers, this drug has the potential to be a therapeutic for many cancer types rather than a specific class.
I’m sure these researchers are working hard to get this into clinical trials, so it remains to be seen how this works in human patients. They have several drugs they’re working with – hopefully one of them will pan out into a useful treatment for cancer patients. May not be a cure, but could definitely be a helpful ally in our fight against this disease.
Thanks & Gig ‘Em.