Researchers have discovered a “viable” new target for the treatment of a particularly aggressive form of breast cancer. The molecule, known as alpha-v-beta-6, could also be used to identify those women with HER2-positive breast cancer who have a higher risk of developing secondary tumors.
The researchers found they could stop cancer cells invading, which these could do only with the help of alpha-v-beta-6 (αvβ6). Using the experimental antibody 264RAD, the team publishing in the Journal of the National Cancer Institute, found they could block the assistance given by the αvβ6 molecule.
Over 2,000 breast cancer patients gave samples for analysis, which revealed that there was no trace of αvβ6 in normal breast tissue but high levels of it in 40% of tumors from HER2-positive patients. The researchers found that the molecule was also a marker of poor chances of survival due to cancer spread.
UK breast cancer research charity the Breast Cancer Campaign, which funded the work, says the results offer hope that an effective treatment could be developed for the group of women with HER2-positive breast cancer who fail to respond to the first-line drug trastuzumab (Herceptin).
Trastuzumab blocks the signals sent from HER2 that promote tumor growth, but “up to 70% of patients either do not respond to Herceptin, or develop a resistance to the therapy,” says the research advocate.
The authors of the research paper add:
“The results of this pre-clinical study suggest that targeting the αvβ6 molecule may enhance the effectiveness of Herceptin – and that a combination treatment could be effective for patients where Herceptin alone has not worked.”
The research was pre-clinical – that is, it was early-stage research that did not test any treatments in humans. Both laboratory cell analyses and tests in mice were undertaken.
The laboratory work analysed the αvβ6 molecule in tissue from breast cancer patients, and the role of αvβ6 in relation to HER2 effects on tumor expression, proliferation, invasion and growth was assessed in the mice.
The mice were randomized to receive 264RAD (the antibody that blocked αvβ6), trastuzumab, or both 264RAD and trastuzumab. This last group with combined blockade of αvβ6 and HER2 showed eradication of the tumors in all the mice treated.
The authors conclude that “simultaneous antibody targeting of αvβ6 (with 264RAD) and HER2 (with trastuzumab) statistically significantly improves the therapeutic effect of trastuzumab alone and statistically significantly increases survival.”
The results on the tissue sample investigations, says Dr. John Marshall, reader in tumor biology at Queen Mary University of London’s Barts Cancer Institute, UK, mean that:
“High αvβ6 levels could be tested for in routine biopsies to identify which women are at a high risk of metastasis, ensuring these women can receive personalised treatment, improving their chances of survival.”
The Medical Research Council also provided grants for the research alongside the Breast Cancer Campaign, whose chief executive Baroness Delyth Morgan says:
“There is a desperate need for drugs which work in new ways to give the thousands of women diagnosed with HER2-positive breast cancer the best possible chances of surviving the disease.
“This study could pave the way for new treatments and bring us closer to our goal of preventing half of the deaths from breast cancer by 2025, through improved and personalised treatments.”
Dr. Marshall and his team are building on their findings by investigating the most effective time to use 264RAD against tumors and potentially stop the spread of HER2-positive breast cancer.
In other recent news about potential new targets for the fight against breast cancer, researchers announcing their results in June 2014 found that a cholesterol-busting compound may halt breast cancer.
Finally, you may be interested in our recent analysis, What is science doing to improve the health and lives of cancer survivors?