New gene shows promise in resistant breast cancer

Researchers have identified a new group of compounds that might one day be added to the armamentarium of therapies designed to fight estrogen-fueled breast cancer. The molecule, called TPBM, and related drugs may have a role in treating patients who have become resistant to other hormone-based therapies, such as tamoxifen.



There are a large number of people who have estrogen receptor-positive breast cancer who respond well to hormone therapy. Sometimes, after a number of years, the hormone therapy stops working. Then they are switched to something else. That works for a time before the cancer progresses.



Exactly what is happening in those cancer cells that they become resistant? Perhaps there is another mechanism that can be overcome and this could be one of them.

Some two-thirds of all breast cancers are estrogen receptor-positive and therefore respond to hormonal treatments such as tamoxifen or the newer aromatase inhibitors, letrozole and anastrozole. Tamoxifen works by blocking estrogen receptors on breast cancer cells, while aromatase inhibitors interfere with the body's ability to produce estrogen.

Many of the cancers in this category eventually become resistant to tamoxifen and, in some cases, tamoxifen may even turn the tables and start acting like estrogen, thereby fueling tumour growth and proliferation.

A new study was presented by researchers from the University of North Carolina, Chapel Hill, the University of Colorado Health Sciences Center, Denver, and the University of Illinois, Urbana-Champaign at the annual meeting of the Endocrine Society, in San Francisco.

Through extensive laboratory testing, they identified a group of compounds related to TPBM that interfered with estrogen's effect on breast cancer cells via a different pathway. The molecules work by affecting the way estrogen receptors interact with a woman's DNA.

TPBM has the advantage of being "highly specific" and therefore potentially much less likely to have any unwanted effects on other cells. It also works against tamoxifen when tamoxifen starts fueling tumour growth. The research is promising, but still preliminary at this stage.

New promise for brain cancer patients with glioblastoma multiforme

Image via WikipediaGlioblastoma multiforme patients could live a year longer by taking the new experimental CDX-110 vaccine from Avant Immunotherapeutics and Pfizer, according to two small Phase II studies presented at the American Society of Clinical Oncology meeting recently.

The vaccine targets the tumour-specific molecule EGFR variant III, which is linked with poor prognosis.

Used with the standard chemotherapy treatment, temozolomide, the vaccine extended the length of life and was also mostly well-tolerated in the Phase II ACTIVATE trial of 21 brain cancer patients and the ongoing ACT II study of 23 patients.

Exclusive global rights to the vaccine were picked up by Pfizer of New York, from Avant Immunotherapeutics of Needham, Mass. in April.

GBM is the most common kind of brain tumour and is very aggressive. Average survival is 13 months to 15 months, with about half of patients dying within that timeframe and a few living two to three years. Those with tumors that express EGFRvIII are extremely unlikely to survive past two years. CDX-110 teaches the immune system to attack EGFRvIII on the tumor.

In the ACTIVATE trial, researchers looked at 21 patients with newly-diagnosed EGFRvIII-expressing GBM who had surgical resection and radiation therapy with oral temozolomide, the standard chemotherapy treatment, and did not have tumor progression. Sixteen patients had three doses of the vaccine at two-week intervals with granulocyte-macrophage colony stimulating factor, while the other five initially had placebo and were later given the vaccine.

Patients who received the vaccine had a median survival of 26 months versus 15.2 months for a matched historical cohort, while median-time-to-progression was 14.2 months compared to 7.13 months. No significant adverse events were reported.

In the similarly designed ACT trial of 23 patients, overall survival with the vaccine was estimated at 33.1 months versus 14.3 months for the matched historical cohort, while time-to-progression was 16.6 months, compared to 6.4 months.

Side effects appeared to be mild and tolerable; some patients experienced redness and itchiness at the injection site, but the side effects did not cause them to discontinue treatment. There were also some mild allergic reactions.

The Phase IIb/III trial was designed to include 90 and then 375 patients and began accruing nine months ago, with enrollment due to complete by year's end and data set for release in 2009. Avant's recently-forged partnership with Pfizer could help speed the trial up and could result in changes to the trial design.