Two specific agents worse than one in treating endocrine resistant breast cancer cells

April 2, 2012

A new class of agents known as c-Src inhibitors is being tested in a number of different ways to treat breast cancer, but researchers at Georgetown Lombardi Comprehensive Cancer Center caution that they should not be used in combination with estrogen to treat endocrine resistant breast cancer.

That's because their new study, being reported at the American Association for Cancer Research (AACR) Annual Meeting 2012, shows that using estrogen and a c-Src inhibitor, PP2, cancel each other out. The benefit once seen in using estrogen was gone once PP2, an inhibitor of the Src-family of kinases used for laboratory studies, was added.

Instead, the findings suggest that using a c-Src inhibitor alone may offer another treatment option to estrogen-receptor-positive whose tumor no longer responds to tamoxifen or aromatase inhibitors, explains the study's lead researcher, Ping Fan, Ph.D. Her research is conducted in the lab of V. Craig Jordan, OBE, PhD, DSc, FMedSci, scientific director at Georgetown Lombardi.

Most c-Src inhibitors have been approved for use in and some are now being tested in solid cancers including . C-Src helps control signaling pathways associated with growth, survival and , and increased activity of this protein has been observed in multiple tumor types.

The study results came about because a Georgetown Lombardi research team, led by Jordan, was testing whether a combination of estrogen and PP2, an inhibitor of c-Src used in laboratory experiments, could work synergistically to destroy that no longer responded to endocrine therapy.

Clinical studies have shown that, for reasons that have not been fully explained yet, about 30 percent of endocrine resistant respond to low doses of estrogen. The Georgetown Lombardi study was designed to see if using PP2 with estrogen could produce a stronger therapeutic outcome.

What they found was unexpected -- there was less, not more, of a killing effect when the two drugs were used together in the lab. Further investigation concluded that c-Src, one of the family of Src kinases inhibited by PP2, "is one of the important molecules in estrogen-stimulated pathways, so using an inhibitor of c-Src eliminates the beneficial effect of estrogen," says Fan.

They also found evidence that estrogen induces expression of multiple genes that act en masse to kill breast cancer cells.

"Our data suggest these two drugs should not be used together in resistant cancers," Fan says.

Explore further: Resistance to anti-estrogen therapy in breast cancer due to natural cell response

Related Stories

Resistance to anti-estrogen therapy in breast cancer due to natural cell response

April 4, 2011
Most breast cancers are fueled by estrogen, and anti-estrogenic agents often work for a time to control the cancers. But many of these cancers become resistant to the drugs for reasons that are not understood, leaving patients ...

Novel approach to treating breast cancer shows great promise

December 7, 2011
In a novel therapeutic approach to treating breast cancer, Loyola University Medical Center researchers are reporting positive results from a clinical trial of a drug that targets tumor stem cells.

Recommended for you

Outdoor light at night linked with increased breast cancer risk in women

August 17, 2017
Women who live in areas with higher levels of outdoor light at night may be at higher risk for breast cancer than those living in areas with lower levels, according to a large long-term study from Harvard T.H. Chan School ...

Scientists develop novel immunotherapy technology for prostate cancer

August 17, 2017
A study led by scientists at The Wistar Institute describes a novel immunotherapeutic strategy for the treatment of cancer based on the use of synthetic DNA to directly encode protective antibodies against a cancer specific ...

Scientists develop blood test that spots tumor-derived DNA in people with early-stage cancers

August 16, 2017
In a bid to detect cancers early and in a noninvasive way, scientists at the Johns Hopkins Kimmel Cancer Center report they have developed a test that spots tiny amounts of cancer-specific DNA in blood and have used it to ...

Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017
New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing ...

Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer

August 16, 2017
In the brief time that drugs known as CDK4/6 inhibitors have been approved for the treatment of metastatic breast cancer, doctors have made a startling observation: in certain patients, the drugs—designed to halt cancer ...

Researchers find 'switch' that turns on immune cells' tumor-killing ability

August 16, 2017
Molecular biologists led by Leonid Pobezinsky and his wife and research collaborator Elena Pobezinskaya at the University of Massachusetts Amherst have published results that for the first time show how a microRNA molecule ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.