FOXD1: The Key to Kidney Tumors?
“Why Kidneys? Why anything else?” For Dr. Oxburgh, a 15-year search for the secret of rejuvenating kidneys may also hold the key to stopping cancer.
“The interesting thing about kidneys is, adult growth just stops,” says Oxburgh. “When kidneys are damaged, the affected tissue simply goes away. With 10% of all adults in the U.S. facing chronic kidney disease, it’s a massive clinical problem.” Working with his team at Maine Medical Cancer Research Institute, Dr. Oxburgh has been seeking new ways to stimulate the body into growing replacement kidney tissue.
“One of the major obstacles to making this happen in adults is that we know many of these growth mechanisms activate cancer- and we don’t want to activate cancer.” says Oxburgh. “We come at this from the opposite point of view than most cancer researchers.” The core of Oxburgh’s research is the study of a particular gene, FOXD1 which appears to regulate the growth of blood vessels surrounding cancer tumors.
“With renal cell carcinoma, one of the really, really fascinating aspects of it is that it forms a new little organ within an organ,” says Oxburgh. “It’s surrounded by this intricate network of blood vessels. We started looking for genetic markers that might control this vessel growth.” It is Dr. Oxburgh’s hope that if FOXD1 can be proven to regulate the growth of these tumors, new targeted gene therapies might be possible- without the damaging side effects of traditional treatments like chemotherapy and radiation.
“It’s a very simple question, but it hasn’t been answered,” says Oxburgh. “It’s only now that we have the capability to do that.”
Cancer cells in the kidney develop many, many blood vessels that feed the growth of tumors and understanding why this happens is one of the keys to improving treatment. This study, lead by Dr. Oxburgh, plans to map a specific gene called FOXD1 that seems to regulate the growth of blood vessels that grow around kidney tumors. The presence of FOXD1 also seems to predict patient survival time and this study seeks to prove that relationship. Eventually, this information could be used to improve treatments for kidney cancer patients by targeting FOXD1 in the tumor.
Understanding the Role of FOXD1 in Renal Cell Carcinoma Angiogenesis
Kidney cancer is the 8th most common cancer in the US. Most kidney cancers are renal cell carcinomas and among these the clear cell type (ccRCC) originating in the proximal tubule is most common. Mutations underlying ccRCC cause cells to engage hypoxic pathways, which signal oxygen deprivation. Because blood vessel ingrowth is an early response to hypoxia, ccRCCs are highly vascularized and blockers of vessel formation are commonly used in treatment. Understanding mechanisms leading to ccRCC vascularization and identifying markers that predict the success of treatment will lead to better therapeutic strategies and improved survival.