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Gene in brain linked to kidney cancer

The commonest form of kidney cancer, clear cell renal cell carcinoma, is fired up by a gene that controls brain growth and development, Mayo Clinic researchers have found.

Sixty to 70 per cent patients can hope to live on for five years if this cancer has not spread to other organs or metastasised. This rate drops drastically to as low as 10 per cent if the cancer spreads.

Published in Cancer Research their study holds the gene NPTX2 primarily culpable for this cancer type, which is resistant to common chemotherapy. The gene is active not only in kidney cancer, but is over-expressed in any human cancer, the study reveals.

“We found that this gene is associated with this most lethal of all urological cancers,” says the study’s senior investigator and molecular biologist John A. Copland, Ph.D.

“We now know what NPTX2 does and how it contributes to cancer progression,” he says. “The study has also thrown up some very promising ideas of how to attack the NPTX2 protein – which may yield a new strategy to treat this, the most deadly of all urological cancers.”

Since the NPTX2 gene is not expressed in normal kidney tissue, a drug targeting its protein could translate into a highly focused treatment, Dr. Copland says.

“It is clear from our study that never before had NPTX2 been seen as a gene that promotes or even plays a role in kidney or any other cancer.” Also, pertinent is the fact that GluR4, a receptor that is targeted usually by the NPTX2 protein in the brain is also found in the kidney cancer samples.

The study shows how NPTX2 and GluR4 promote cancer growth and metastasis. The over-expressed NPTX2 protein is secreted from the cell and then attaches itself to GluR4 on the kidney cancer cell membrane.

NPTX2 glues multiple GluR4 proteins into a channel that leads into the cell, creating a path for calcium to flow in. “The elevated levels of calcium triggers multiple signalling pathways that promote cell doubling and survival and changes in the cell that promote cancer invasion and metastasis,” says Dr. Copland.

By blocking the GluR4 channels the researchers were able to cause the cancer cells to die, pointing to a possible avenue for therapy. Since NPTX2 was expressed in all stages of kidney cancer, especially metastasis, it is clear that it plays an important role in tumor development and progression. Its expression could be used as a biomarker test to ensure patients benefit from an NPTX2 inhibitor, when one is developed.

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