Kidney Ca data could help individualize treatment

Researchers at UCLA’s Institute of Urologic Oncology and department of urology have classified kidney cancer into several unique subtypes, a finding that could help physicians tailor treatment to individual patients.

The finding is the result of 10 years of research by the investigators, who have studied kidney cancers at the genetic and molecular levels and conducted chromosomal analyses in an effort to identify what mutations may be causing and affecting the behavior of the malignancies. Thousands of tumors removed at UCLA have been studied, said senior author Allan Pantuck, MD.

"Pathologists can give us some important information, but similar-appearing tumors often can and do behave differently," Dr. Pantuck said. "Our findings have us heading further in the direction of personalized medicine based on the molecular signature of an individual’s tumor. We still have a lot to learn, but we’re now a step closer."

In this study, which was published online in Cancer (April 16, 2013), the authors found that in clear cell renal cell carcinoma, there were deletions of the short arm of chromosome 3 and the long arm of chromosome 14. Most of the tumors examined had lost chromosome 3p, while a further subgroup among the tumors also had lost chromosome 14q.

This is significant because the short arm of 3p harbors a tumor suppressor gene. In the case of chromosome 14q, losing it results in the additional loss of a hypoxia-inducible factor 1 (HIF1) alpha gene, which mediates the effects of hypoxia on the cell.

The authors found that the loss of chromosome 3p was associated with improved survival, meaning these tumors might not need to be treated as aggressively as tumors without loss of chromosome 3p, or the tumors could perhaps be monitored aggressively in elderly patients for evidence of progression instead of receiving immediate treatment. In tumors that lost both chromosome 3p and chromosome 14q, the patients had much worse outcomes.

"The results of this study support the hypothesis that the HIF1 alpha gene functions as another important tumor suppressor gene," Dr. Pantuck said. "With this finding, we can now decide to treat these patients with more aggressive therapies."

Going forward, Dr. Pantuck and his team will work to identify more subtypes of kidney cancer. The findings also come from a single center, so they will need to be reproduced by other scientists, he said.