Gene key to common kidney cancer identified

Washington, May 21 (ANI): Scientists have found a key gene that, when turned off, promotes the development of common kidney cancer.

Their findings suggest that a combination of agents now being tested in other cancers may turn the gene back on, providing a much-needed therapy for the difficult-to-treat cancer.

Researchers at Mayo Clinic”s campus in Florida describe a gene called GATA3 that has been silenced in clear cell renal cell carcinoma (ccRCC), the most common kind of kidney cancer, and is a key gene also lost in breast cancer.

GATA3 controls many genes and proteins that regulate cell growth, and one of them, a receptor known as the type III transforming growth factor-ß receptor (TßRIII), is absent in a number of cancers.

According to the study”s senior investigator, John Copland, a cancer biologist at the Mayo Clinic campus at Florida, these findings will surprise many in the cancer field.

“Cancer researchers know that GATA3 is essential for immune T cell development and function. As well, very recent studies show that GATA3 is also critical to breast cancer development, where GATA3 expression is limited to mammary luminal epithelial cells. GATA3 is lost during breast cancer progression and its loss is a strong predictor of poor clinical outcome in luminal breast cancer. GATA3 also plays an important role in renal development and differentiation during embryogenesis, but little is known about the role of GATA3 in the adult human kidney,” he said.

“Now it looks like GATA3 regulates the expression of genes that are critical to cancer control in the kidney, and silencing it appears to be very important to the growth of kidney cancer and probably to others tumors, as well. No one could have guessed that would be the case in kidney cancer. This is a completely novel finding,” he added.

The study has been published in the May 20, 2010 issue of Oncogene. (ANI)

Scientists find genetic secrets to common kidney cancer

Washington, May 19 (ANI): Researchers at Mayo Clinic”s campus in Florida have discovered genetic secrets to common kidney cancer.

By examining expression of every human gene in clear cell renal cell carcinoma (ccRCC) compared to normal kidney cells, researchers have discovered gene signatures that explain much of the biology of this common and difficult-to-treat kidney cancer.

The researchers say they have found: a biological pathway signature of ccRCC for a group of altered genes that give this distinct cancer its “clear cell” appearance; other genes that confer stem cell-like properties to the cancer; and a set of master genes lost in ccRCC that they believe likely pushes initial development of the cancer.

“Understanding these genes and the pathways they regulate could provide valuable insight into how to treat ccRCC,” said hematologist/oncologist Han W. Tun, the study”s first author.

This cancer makes up 80 percent of all kidney cancer and is often resistant to both chemotherapy and radiation treatment, Dr. Tun said.

Senior investigator John Copland, a cancer biologist, said: “Up until this point, ccRCC was largely a mystery, but now we have new and exciting clues that seem to reveal the origin and development of this cancer.”

The study appears in the May 18 issue of PLoS ONE. (ANI)

Experimental drug turns on tumour suppressor gene to halt cancer cell growth

Washington, January 21 (ANI): A study conducted by Mayo Clinic researchers has shown that an experimental drug can turn on a powerful tumour suppressor gene to halt the growth of cancer cells.

The researchers revealed that they made this finding while testing the drug for its efficacy to treat a deadly form of thyroid cancer.

According to them, few other cancer drugs have this property.

Describing their study in the journal Cancer Research, the researchers said that RS5444, being tested in a Phase 1/2 clinical trial to treat anaplastic thyroid cancer, might be useful for treating other cancers.

The agent is also known as CS-7017, according to their report.

Previous studied had already shown that RS5444 binds to a protein known as PPAR-gamma, a transcriptional factor that increases the expression of many genes.

The researchers said that past research had shown that human anaplastic thyroid tumour cells treated with RS5444 expressed a protein known as p21, which inhibited cell replication and tumour growth.

However, they added, the underlying factor behind that effect was unknown.

The team claimed that they had discovered that the agent actually forces PPAR-gamma to turn on the RhoB tumour suppressor gene, which in turn induces p21 expression.

“This is very unusual. Drugs typically target genes and proteins that are over-expressed and turn them off. We found that RS5444 turns on a valuable tumour suppressor gene. We rarely find a drug that can take a suppressed gene and cause it to be re-expressed,” says the study’s lead investigator, Dr. John Copland, a cancer biologist at the Mayo Clinic campus at Jacksonville.

Study co-author Dr. Robert Smallridge, who treats thyroid cancer patients at Mayo Clinic in Jacksonville, says that the finding suggests that other cancers in which RhoB is deactivated might respond to RS5444 or to similar drugs.

“This study provides a hint that this class of drugs could have a significant effect on cancer biology because of its action on this tumour suppressor gene,” says Dr. Smallridge.
Dr. Copland adds: “RS5444 and other so-called PPAR-gamma drugs, which were originally created to treat diabetes because they help regulate glucose metabolism, are in development or being tested as cancer therapies. Taken orally, RS5444 requires 1,000-fold less dosage than current Food and Drug Administration-approved drugs in this class of compounds to inhibit tumor growth.”

The researchers have been seeking to identify and characterize the molecular mechanisms underlying the cause and progression of human anaplastic thyroid carcinoma, and their goal is to develop effective molecular targeted therapies. (ANI)