Breast Cancer Treatment On The Horizon

Researchers find gene necessary for tumour growth

HAMILTON (CUP) — A team of researchers at McGill and McMaster universities may have discovered a way to treat breast cancer. The team extracted fragments of tumorous tissue from breast-cancer-prone mice and used recombinant technology to remove the beta1-integrin gene.

“We are the first to demonstrate the requirement for beta1-integrin in the induction of breast cancer in genetically engineered mice,” William Muller, a researcher at the McGill health centre, told the McMaster Daily News, a university public affairs publication. “Our findings show that blocking the function of this gene halts tumour proliferation. We also show that in our model of breast cancer, tumour cells do not grow without beta1-integrin.”

Muller, along with his colleagues John Hassel, Natasza Kurpios and Donald White from the biochemistry and biomedical sciences departments at McMaster University, demonstrated the removal of the gene did not affect the normal mammary development of their animal subjects, while preventing new tumours from growing.

Although developing a treatment for breast cancer is the most promising application of this discovery, it may also have applications for other cancers, including prostate, ovarian, and colon cancers.

The Canadian Cancer Society estimates 21,200 women will be diagnosed with breast cancer and 5,200 will die from it this year. Incidence rates for breast cancer have stabilized since 1990, and death rates have decreased since 1990. But breast cancer remains the cancer most frequently diagnosed in women.

The McMaster and McGill researchers have not begun testing on humans. Kurpios says before they apply their findings to human therapy, they have to identify the function of the beta1-integrin gene in normal cells.

“This protein plays an important developmental function” in mice, said the McMaster researcher. “This will be critical for developing drug targets that will not harm the patients.

“Breast cancer research has entered a period of rapid growth in the development of highly specific and effective anti-cancer drugs,” Kurpios said. “As these drugs target proteins and their associated pathways important for normal development, new challenges will need to be addressed to minimize toxicity to the patient.” Popular treatments for breast cancer, such as Herceptin, can result in severe hypersensitivity reactions, infusion reactions and pulmonary events. However, these reactions are rarely fatal.

“Modelling human cancer in a genetically engineered mouse will serve as a valuable tool to identify phenotypes upon genetic manipulation and predict side effects unique to cancer treatment,” Kurpios said. The researcher added: “More detailed analysis of these mouse models is needed to better understand cancer and develop strategies to treat it.”

Their pre-clinical research is expected to generate the development of effective drugs that will block or even prevent the development of breast cancer. Muller anticipates a possible treatment for breast cancer will appear in about five years. The primary tumour is not what kills its victims, Kurpios explained, but rather its metastases, or secondary cancerous growth, which forms away from the initial tumour.

“Effective therapeutics should target cell-surface molecules specifically expressed by metastasis of breast cancer,” Kurpios said. “The characterization of metastases in transgenic mice models of human breast cancer will be crucial and will constitute the future direction of cancer research.”

The findings were published in the August 23 issue of the journal Cancer Cell.