By Drs Mark Boyd, Nikolina Vlatkovic and Mr Keith Parsons.
Cancers of the kidney are on the increase in the developed world. In the UK, the number of cases has doubled in the past thirty years with over 9,000 new cases diagnosed in 2010 and 4,000 patients now dying from this disease each year.
One of the key questions we are trying to find the answer to is: why do some kidney cancers kill patients when others that are apparently similar, do not.
To understand this we have focused in a recent study which we published in the British Journal of Urology International on two genes, called p53 and MDM2, that we know play an important role in a wide range of cancers. Normally there is a carefully controlled balance between these two genes.
However, our study showed for the first time that in Kidney cancer cells this balance is lost and that this occurs in a most unusual way. Normally, the p53 gene is important to prevent cancer with one of its jobs being to kill potentially dangerous cells that could develop into cancers. The role of MDM2 is to balance this so that p53 only kills the right cells. In most other types of cancer, the ability of the p53 gene to kill dangerous cells stops working because of changes in the genetic material, literally mutations in the DNA sequence that spell out what the p53 gene does.
However, in kidney cancers this does not happen and the p53 gene is, apparently, quite normal. What seems to happen is that in kidney cancer cells, the p53 gene is normal, BUT it does not perform the cancer protective function and part of this is connected to MDM2. Our MKF-funded studies are focusing on understanding what happens to these vital pathways in kidney cancers. Since both p53 and MDM2 are being examined as potential drug targets by some of the world’s largest drug companies, we need to understand more about what is happening in kidney cancer cells so that we can develop strategies that focus on these genes that will ultimately benefit patients with this disease.