A single gene appears to play a crucial role in deadly breast cancers, increasing the chances the cancer will spread and making it resistant to chemotherapy, US researchers report.
They found people with aggressive breast cancers have abnormal alterations in a gene called MTDH, and drugs that block the gene could keep local tumours from metastasising or spreading, increasing a woman's chances for survival."Not only has a new metastasis gene been identified, but this also is one of a few such genes for which the exact mode of action has been elucidated," said Dr Michael Reiss of The Cancer Institute of New Jersey in New Brunswick, whose study appears in the journal Cancer Cell.
"That gives us a real shot at developing a drug that will inhibit metastasis," he said in a statement.
Stopping cancer's spread is important - while more than 98% of patients with breast cancer that has not spread live five years or more, only 27% of patients whose cancer has spread to other organs survive.
How the gene was found
Reiss and Yibin Kang of Princeton University used several different research approaches to find the gene, which helps tumour cells stick to blood vessels in distant organs.
To get them in the right general area, they used big computer databases of breast tumours and found that a small segment of human chromosome 8 was repeated many times in people with aggressive breast tumours.
While most normal DNA sequences contain only two copies of a gene, they found some breast tumours had as many as eight copies of this gene segment.
The team then turned to human breast tumour samples taken from 250 patients to look for these genetic abnormalities and found the gene MTDH was overly active or expressed in aggressive tumours.
Exists in every cell
"This gene exists in every one of our cells," Kang said in a telephone interview. "Somehow the tumour gains extra copies and overexpresses them.
"We saw 30% to 40% of them overexpressed this gene."
The researchers then injected lab mice with tumour cells from patients who had this genetic alteration and found the mice formed tumours that were more likely to spread.
They also were more likely to resist treatment with traditional chemotherapy drugs, such as paclitaxel (Anzatax, Taxol, Biolyse Paclitaxel, Teva-Paclitaxel).
But when they genetically altered these tumours, inhibiting the MTDH gene, the tumour cells were less able to spread and were more vulnerable to chemotherapy.
May lead to new drugs
Kang said he is hopeful the finding will lead to drugs that not only keep breast cancer from spreading, but also make it more responsive to treatment.
"If we have a drug to inhibit this type of gene, one stone hits two birds," Kang said.
He said MTDH may also play a role in other types of cancers, including prostate cancer. "It's likely to be a broad influence gene," he said.
Kang said he thinks it would be possible to develop an antibody to neutralise the activity of the gene.
Already, it has gained the attention of drug makers. Kang said he plans to meet with Johnson & Johnson next week.
"I'm quite optimistic we will try to develop a drug as quickly as possible," he said.
(Reuters Health, January 2009)