NIH Press Release - RESEARCHERS DISCOVER METHOD IN MICE TO RESTORE TAMOXIFEN SEN

[Guest guest]

fyi...

U.S. Department of Health and Human Services

NATIONAL INSTITUTES OF HEALTH

NIH News

NIH Office of the Director (OD)

http://www.nih.gov/icd/od/>

National Cancer Institute (NCI)

http://www.nci.nih.gov/>

Embargoed for Release: Monday, December 11, 2006 12:00 noon ET

CONTACT: NCI Media Relations Branch, ,

ncipressofficers@...>

RESEARCHERS DISCOVER METHOD IN MICE TO RESTORE TAMOXIFEN SENSITIVITY

IN RESISTANT BREAST CANCER

The widely used breast cancer drug tamoxifen (Nolvadex®), which can

become less effective over time, might retain its full strength

indefinitely if used along with a second drug, according to new

research in mice conducted by investigators from the National Cancer

Institute (NCI), part of the National Institutes of Health, and their

partners. The results appear in the December 11, 2006, issue

of " Cancer Cell " *.

Tamoxifen has been used successfully since the 1970s to treat certain

types of breast cancer and to prevent them from recurring after

surgery. Clinicians observed that tamoxifen treatment initially

reduced the rate of recurrence by nearly 50 percent. Over time,

however, patients develop resistance to the drug and tamoxifen loses

its effectiveness as a cancer treatment.

" Tamoxifen has been extremely important in the management of breast

cancer, " said NCI Director E. Niederhuber, M.D. " Being able to

overcome resistance would be an important advance. "

In the study, the research team, led by Farrar, Ph.D., of

NCI's Center for Cancer Research at Frederick, Md., found that the

effectiveness of tamoxifen in cell cultures and in mice can be fully

restored by the use of a compound called disulfide benzamide, or

DIBA. The investigators confirmed their study hypothesis about

DIBA's effect on tamoxifen resistance by using the compound in mice

that were engineered to have tamoxifen-resistant tumors and saw that

tumor growth was reduced by nearly 50 percent when DIBA was

administered.

" Exposure to DIBA causes certain physical changes to occur between

the estrogen receptor and the biological machinery that stimulates

cell division. By coincidence, these changes also restore the

estrogen receptor to a form that makes it vulnerable once again to

tamoxifen, " said Li Hua Wang, Ph.D., lead author of the study.

Some, but not all, breast cancer cells have specific receptors that

bind estrogen molecules circulating in the bloodstream. When estrogen

binds to the estrogen receptor, it triggers a series of events that

promote cell division. If the cell is a breast cancer cell, this

interaction leads to tumor growth. In women with estrogen receptor-

positive cancers, cancer cell growth is strongly influenced by

estrogen.

Tamoxifen works by binding to estrogen receptors in place of estrogen

and blocking the signals that lead to cell division. Initially, tumor

growth slows or stops altogether. With continued tamoxifen treatment,

however, the estrogen receptor and the estrogen-dependent signaling

pathways in the cell can become altered, rendering tamoxifen

ineffective as an inhibitor. In some cases, tamoxifen begins to act

like estrogen and can stimulate tumor growth.

DIBA and related compounds are being studied because of their ability

to disrupt cellular activity at the genetic level. These so-called

electrophilic compounds were first investigated for possible use

against AIDS because they can block the human immunodeficiency virus

(HIV) from replicating. The HIV studies are ongoing.

" This basic study generated exciting results in our mouse model and

suggests a promising approach that might be tried in human patients, "

said Farrar. His laboratory is now exploring ways to produce DIBA in

a form that is water soluble so it could be administered as a pill,

the same as tamoxifen. If successful, this could set the stage for

preclinical studies.

[Guest guest]

thank you for this interesing article, as i am having great problems on tamo or

armi i asked my onc what did they do before the drugs were around, his reply was

that they used to remove women`s ovaries to decrease the estrogen, i cannot find

a web page that has the stats on how many women survied back before these drugs,

does anyone know any facts??

hugs sandy in oz

marisa msteffers@...> wrote:

fyi...

U.S. Department of Health and Human Services

NATIONAL INSTITUTES OF HEALTH

NIH News

NIH Office of the Director (OD)

National Cancer Institute (NCI)

Embargoed for Release: Monday, December 11, 2006 12:00 noon ET

CONTACT: NCI Media Relations Branch, ,

RESEARCHERS DISCOVER METHOD IN MICE TO RESTORE TAMOXIFEN SENSITIVITY

IN RESISTANT BREAST CANCER

The widely used breast cancer drug tamoxifen (Nolvadex®), which can

become less effective over time, might retain its full strength

indefinitely if used along with a second drug, according to new

research in mice conducted by investigators from the National Cancer

Institute (NCI), part of the National Institutes of Health, and their

partners. The results appear in the December 11, 2006, issue

of " Cancer Cell " *.

Tamoxifen has been used successfully since the 1970s to treat certain

types of breast cancer and to prevent them from recurring after

surgery. Clinicians observed that tamoxifen treatment initially

reduced the rate of recurrence by nearly 50 percent. Over time,

however, patients develop resistance to the drug and tamoxifen loses

its effectiveness as a cancer treatment.

" Tamoxifen has been extremely important in the management of breast

cancer, " said NCI Director E. Niederhuber, M.D. " Being able to

overcome resistance would be an important advance. "

In the study, the research team, led by Farrar, Ph.D., of

NCI's Center for Cancer Research at Frederick, Md., found that the

effectiveness of tamoxifen in cell cultures and in mice can be fully

restored by the use of a compound called disulfide benzamide, or

DIBA. The investigators confirmed their study hypothesis about

DIBA's effect on tamoxifen resistance by using the compound in mice

that were engineered to have tamoxifen-resistant tumors and saw that

tumor growth was reduced by nearly 50 percent when DIBA was

administered.

" Exposure to DIBA causes certain physical changes to occur between

the estrogen receptor and the biological machinery that stimulates

cell division. By coincidence, these changes also restore the

estrogen receptor to a form that makes it vulnerable once again to

tamoxifen, " said Li Hua Wang, Ph.D., lead author of the study.

Some, but not all, breast cancer cells have specific receptors that

bind estrogen molecules circulating in the bloodstream. When estrogen

binds to the estrogen receptor, it triggers a series of events that

promote cell division. If the cell is a breast cancer cell, this

interaction leads to tumor growth. In women with estrogen receptor-

positive cancers, cancer cell growth is strongly influenced by

estrogen.

Tamoxifen works by binding to estrogen receptors in place of estrogen

and blocking the signals that lead to cell division. Initially, tumor

growth slows or stops altogether. With continued tamoxifen treatment,

however, the estrogen receptor and the estrogen-dependent signaling

pathways in the cell can become altered, rendering tamoxifen

ineffective as an inhibitor. In some cases, tamoxifen begins to act

like estrogen and can stimulate tumor growth.

DIBA and related compounds are being studied because of their ability

to disrupt cellular activity at the genetic level. These so-called

electrophilic compounds were first investigated for possible use

against AIDS because they can block the human immunodeficiency virus

(HIV) from replicating. The HIV studies are ongoing.

" This basic study generated exciting results in our mouse model and

suggests a promising approach that might be tried in human patients, "

said Farrar. His laboratory is now exploring ways to produce DIBA in

a form that is water soluble so it could be administered as a pill,

the same as tamoxifen. If successful, this could set the stage for

preclinical studies.