Four key genes leading to breast cancer metastasis found--2 already blockable

[Lani]

d Printable version
Key to breast cancer spread found

Breast cancer cells can spread to other parts of the body
Scientists have come closer to working out what makes breast cancer deadly.
Four genes have been found to work together to drive the spread of breast cancer to the lungs.

Turning off all four genes at once dramatically reduces the ability of breast tumours to spread - or metastasise - a study in mice showed.

Reporting the results in Nature, the US team said they were planning clinical trials of drugs known to target two of the genes in the set.

Tumours spread when cancer cells break away and travel through the bloodstream to a different site in the body - a process called metastasis.


This really nailed the case that if we can inactivate these genes in concert, it will affect metastasis
Dr Joan Massague

It is the ability to spread to other tissues and organs that makes cancer potentially deadly and metastases are very common in the late stages of cancer.

In a series of experiments, Dr Massague found that four of those genes which produce proteins which combine to enable cancer cells to escape into the bloodstream and get into the lungs.

Knocking out each of the genes individually in human cancer cells that had been implanted in mice had a small effect on cancer growth and metastasis.

But turning off all four genes at once almost eliminated tumour growth and spread, and the tangle of blood vessels that is normally seen in a tumour was greatly reduced.

Injecting cancer cells that had all four genes turned off into the bloodstream of mice also showed that the cells lacked the ability to get into lung tissue.

Treatment

Two drugs known to inhibit two of the proteins produced by the genes - cetuximab and celecoxib - were also shown to reduce the growth and spread of the breast tumours in mice if used in combination.

Discussions are underway for clinical trials in humans.

Dr Massague, chair of the cancer biology and genetics programme at Memorial Sloan-Kettering Cancer Center said: "We found that the combination of these inhibitory drugs was effective even though the drugs individually were not very effective.

"This really nailed the case that if we can inactivate these genes in concert, it will affect metastasis."

"These genes are used together to attract blood vessels and enter the blood stream and then once they reach the lung they use the same strategy to enter the lungs."

Cancer spread

Dr Massague is also looking at which genes promote metastasis to other sites in the body, such as brain and bone and whether the same or similar genes are involved in cancer spread in other cancer types, such as colon cancer.

Dr Anthea Martin, cancer information officer at Cancer Research UK, said: "Cancer's ability to spread around the body can make the disease difficult to treat.

"This research has added to our knowledge of the genes that may be involved in the spread of breast cancer to the lungs.

"The more we understand about this process, the more likely it is that scientists will be able to design treatments to prevent it from happening.

"It is not known

[Lani]

Last Updated: Wednesday, 11 April 2007, 23:23 GMT 00:23 UK

E-mail this to a friend Printable version
Key to breast cancer spread found

Breast cancer cells can spread to other parts of the body
Scientists have come closer to working out what makes breast cancer deadly.
Four genes have been found to work together to drive the spread of breast cancer to the lungs.

Turning off all four genes at once dramatically reduces the ability of breast tumours to spread - or metastasise - a study in mice showed.

Reporting the results in Nature, the US team said they were planning clinical trials of drugs known to target two of the genes in the set.

Tumours spread when cancer cells break away and travel through the bloodstream to a different site in the body - a process called metastasis.


This really nailed the case that if we can inactivate these genes in concert, it will affect metastasis
Dr Joan Massague

It is the ability to spread to other tissues and organs that makes cancer potentially deadly and metastases are very common in the late stages of cancer.

In a series of experiments, Dr Massague found that four of those genes which produce proteins which combine to enable cancer cells to escape into the bloodstream and get into the lungs.

Knocking out each of the genes individually in human cancer cells that had been implanted in mice had a small effect on cancer growth and metastasis.

But turning off all four genes at once almost eliminated tumour growth and spread, and the tangle of blood vessels that is normally seen in a tumour was greatly reduced.

Injecting cancer cells that had all four genes turned off into the bloodstream of mice also showed that the cells lacked the ability to get into lung tissue.

Treatment

Two drugs known to inhibit two of the proteins produced by the genes - cetuximab and celecoxib - were also shown to reduce the growth and spread of the breast tumours in mice if used in combination.

Discussions are underway for clinical trials in humans.

Dr Massague, chair of the cancer biology and genetics programme at Memorial Sloan-Kettering Cancer Center said: "We found that the combination of these inhibitory drugs was effective even though the drugs individually were not very effective.

"This really nailed the case that if we can inactivate these genes in concert, it will affect metastasis."

"These genes are used together to attract blood vessels and enter the blood stream and then once they reach the lung they use the same strategy to enter the lungs."

Cancer spread

Dr Massague is also looking at which genes promote metastasis to other sites in the body, such as brain and bone and whether the same or similar genes are involved in cancer spread in other cancer types, such as colon cancer.

Dr Anthea Martin, cancer information officer at Cancer Research UK, said: "Cancer's ability to spread around the body can make the disease difficult to treat.

"This research has added to our knowledge of the genes that may be involved in the spread of breast cancer to the lungs.

"The more we understand about this process, the more likely it is that scientists will be able to design treatments to prevent it from happening.

"It is not known if the same genes are involved in the spread of all cancers, but this work is a great starting point for scientists looking at this important area of research."

Thanks Lani, for this post and the earlier post. You're much better than Google Alert.

[Caroline UK]

I'm happy to hear about this, Lani, thanks so much for telling us. I'll ask my oncologist about it next week. There seems to be a lot of work going on, thank you scientists is all I can say, it gives me hope and that's very precious.

[LindaC]

Lani,
Thanks for the info.I am seeing my onc. tomorrow.

[Soccermom]

Dear Lani, Here's the link...

http://www.nature.com/cgt/journal/v1.../7701027a.html

Warmly,Marcia

[Soccermom]

Lani,
Just recieved this blurb tonight...FYI..

This company, Apthera, has a breast cancer vaccine called neuvax to help prevent cancer recurrence if you're HER2-positive. The phase II clinical trial results are posted on their website stating, "At this point, clinical recurrence rates at 24 months are 5.6% (5/90) for vaccinated patients versus 14.8% (12/81) for the observation group (p=0.04)." The vaccine was originally developed at MD Anderson.

The treatment is going to start phase III trials this year... Their website is: www.apthera.com.

When you have a minute please review, Thanks for all your research!
Marcia

[futurefocus]

I must agree...you are better than goggle...you have such an expertise ...maybe you are a doctor...thnaks for all your postings...I learn something every time I read them.

[Lani]

I heard Dr. Peoples present his results at two conferences, the most recent in San Antonio in December. His results are very immature (early on, when many patients may not have been expected to have recurred anyway) and on quite a small number of patients.

I know a while back he was trying to get permission to start a trial where the patients were allowed to have both Herceptin and the vaccine, but hadn't heard if he ever was able to.

Best articles/talks I have read/heard on breast cancer vaccines were by Keith Knutson (I think that is how his name is spelled) of the Mayo Clinic

All I can tell you is that from my reading
Immunology is another area where what is understood is miniscule in relation to what is not. I would not even dare to venture any type of opinion in the area. I am certainly not qualified to and the only thing I am certain of is that I don't have enough knowledge to.


If you are in California, I know of one oncologist who is also an immunologist, who has won awards/prizes on immunological aspects of cancer, Ellie Guardino of Stanford. Perhaps she or Dr. Knutson would be good people to ask (or Mary Disis of Seattle whom Lolly writes about)

Do any of you know these oncologists well enough to ask their opinion?