January 9, 2008 / 6:48 PM / 11 years ago

Missing molecules key to breast cancer spread

CHICAGO (Reuters) - By restoring tiny bits of genetic material missing from breast tumors in mice, U.S. researchers said on Wednesday they were able to block the cancer’s ability to spread.

A doctor examines a breast x-ray in an undated file photo. By restoring tiny bits of genetic material missing from breast tumors in mice, U.S. researchers said on Wednesday they were able to block the cancer's ability to spread. REUTERS/National Cancer Institute/Handout

The finding will help doctors make better treatment decisions and may give rise to a new way of halting the advance of breast cancer, said Dr. Sohail Tavazoie, an oncologist at Memorial Sloan-Kettering Cancer Center in New York.

“What’s most important to us as cancer doctors is the concern that the cancer is going to come back,” said Tavazoie, whose study appears in the journal Nature.

Tavazoie said the research will give doctors a better way to determine if a particular breast cancer tumor will spread and also add to the list of possible targets that could be used to make drugs that block genes that make cancers spread.

And down the road, it may lead to new therapies that restore the missing molecules that keep cancer tumors in check.

Cancer spreads when bits the primary tumor break off and attack other organs. This process, known as metastasis, is what makes cancer so deadly.

LIKE ORCHESTRA CONDUCTORS

Tavazoie, working in the lab of Joan Massague, a Howard Hughes Medical Institute researcher, set out to isolate the process that causes aggressive tumors to spread.

They found bits of genetic material called ribonucleic acid or RNA that suppress the spread of breast cancer to the lungs and bone. When they put those molecules back into breast cancer tumors in mice, the tumors lost their ability to spread.

Tavazoie said these small pieces of RNA known as microRNAs work by directing the activity of genes, much like the conductor of an orchestra.

They found that in certain aggressive cancers, some of these microRNAs are missing, allowing the aggressive spread of the cancer. When they restored these microRNAs to human breast cancers in laboratory mice, the cancer stopped spreading.

The researchers also found these same microRNAs were missing from human breast cancer cells taken from women whose tumors had spread.

“We think these microRNAs will help us to know if this is an aggressive tumor or not,” Tavazoie said in a telephone interview.

“If it is, we will need to treat this woman with very aggressive therapy and we will need to be diligent about watching it,” he said, adding that it may help doctors decide whether some women with less aggressive tumors can skip chemotherapy.

Tavazoie’s team also looked to see which genes were causing all of the trouble when the microRNAs went missing. They found an especially strong association between the loss of miR-335 and cancer relapse. When this microRNA was absent, they found strong activity in a set of six genes.

Two of the genes, SOX4 and TNC, were already known to play a role in cell migration. When the researchers suppressed the activity of these genes, they reduced the cancer’s ability to spread.

Editing by Maggie Fox and Xavier Briand

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