New targeted treatment promising in breast cancer

By Martha Kerr

NEW YORK (Reuters Health) - An novel investigational chemotherapy regimen targeting both a mutated protein called p53 and tumor blood vessels "has complementary and potent antitumor activity and could define a new strategy for suppression of advanced breast cancers," Dr. Yayun Liang reported at the Department of Defense's annual Era of Hope breast cancer meeting that just wrapped in Baltimore, Maryland.

In half of all breast cancer cases, mutated p53 protein is present. Previous research has indicated that when p53 is mutated, tumor cells are prolific and develop quickly. PRIMA-1, a small molecular drug, targets and returns normal function to the mutated p53, but PRIMA-1 alone is not enough to halt tumor growth. Proliferating blood vessels supply oxygen and other nutrients that fuel tumor growth. However, a monoclonal antibody called 2aG4 can selectively shutdown these tumor blood vessels and prevent future growth.

Liang, of the University of Missouri at Columbia, and colleagues tested the combination of PRIMA-1 and 2aG4 in two tumor cell lines containing mutated p53.

The regimen "suppressed tumor growth additively, leading to complete arrest of tumor progression during treatment," Liang said. "Some tumors were completely eradicated...and combination treatment led to synergistic loss of tumors."

The combination therapy has "potent anti-tumor activities" in breast cancer cells that produce the Her2 protein as well as in those that do not. At least 25 percent of breast cancers produce the Her-2 protein, which is known to be a marker for poor prognosis.

In an interview with Reuters Health, Liang explained that targeted therapy, such as the PRIMA-1/2aG4 combination being tested, "specifically targets tumors and has less toxicity to normal cells or organs. The conventional chemotherapy is less specific and more toxic."

"I believe the proposed combination therapy will move to clinical trials in the near future," she said.