One step forward in cancer treatments

Dr. Stefan Roberts, a professor in the Department of Biology at UB, has played a part in possibly advancing cancer treatment. By linking an enzyme to the breakdown of a specific protein in cancerous cells, it may be possible to lower the necessary amount of chemotherapy needed to treat cancerous tumors.
The protein known as WT1 is found in many cancerous tumors. WT1 stands for 'Wilms' Tumor 1,' which is a gene that codes for the protein critically involved in the normal development of the urogenital system. A childhood kidney cancer called 'Wilms' Tumor,' or nephroblastoma, is associated with a mutation in the genes for the WT1 protein, hence the name. In this cancer and also in childhood leukemia, the WT1 acts as a tumor suppressor.
'WT1 is kind of a bit of a Janus – it has two heads to it, one of them is not very nice, and one of them is nice. And it depends what tumor you're looking at,' Roberts said when referring to the fact that the WT1 protein can sometimes act as a tumor suppressor and at other times act as an oncogene, a gene that stimulates cancer proliferation.
By using cultures of human cancer cell lines that express WT1, Roberts and his colleagues were able to discover what happens when cancer cells are treated with HtrA2, an enzyme that breaks down proteins. By linking WT1 with this enzyme, they have discovered that it has the capability of degrading WT1.
In some cancers, WT1 needs to be degraded in order for cells to die on time, undergoing a process called apoptosis. It appears that in many adult cancers, WT1 helps the cancer continue to reproduce, but in some childhood cancers the WT1 acts as a tumor suppressor. Therefore, the elimination of WT1 in many adult tumors would slow the growth of the cancer. This means that the rate at which cancer cells die would increase because of the addition of HtrA2.
This finding has implications for patients regarding chemotherapy. The cytotoxic drug administered during treatment 'damages DNA, inhibits cell division, and generally targets dividing cells,' according to Roberts.
This includes cancerous cells, of course, but it also includes the digestive lining, hair cells and skin cells, which is why people undergoing chemotherapy often lose their hair and have skin and digestive system complications.
'If we eliminated the WT1 from the cells [of certain cancers], you need to take less drugs to kill them. So the idea … is that if you can target things that stack the odds towards the cell undergoing apoptosis, then that can only be a good thing,' Roberts said.
This would reduce the amount of chemotherapy needed to treat an individual's cancer, meaning that there would be fewer side effects. Fewer side effects are imperative in childhood cancer because chemotherapy makes children so sick for such a long time. Being so ill often disturbs kids' progress in school, among other things.
A problem with chemotherapy is that most times, it ends up causing DNA damage in healthy cells along the way, which can cause secondary cancers years later that result from the original treatment of chemotherapy. The less chemotherapy children undergo, the better chance they have at leading a longer, healthier and cancer-free life.
'This is not a cure for cancer by any means, but it is something you really want to go check out now because these agents are basically degrading a protein that in one cancer is a good thing, but in another tumor might not be a good thing and make the treatment less effective,' Roberts said.
This gives hope to the eventual use of this enzyme on real patients in order to reduce the amount of chemotherapy for certain types of cancers.

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