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Two-hit therapy eradicates breast tumor in mice

Researchers at the Perelman School of Medicine, University of Pennsylvania (PA, USA) have eradicated a specific type of breast cancer in mice by administering anti-erbB2/neu antibody treatment followed by interferon-gamma therapy.

The findings, published in Cell Reports, could lead to improvements in current treatments for HER2-positive breast cancers and a reduction in the amount of cancer drugs used.

Currently, single agent anti-erbB2/neu monoclonal antibody-based drugs such as trastuzumab are only effective in 30% of breast cancer patients, yet are often combined with chemotherapy to improve efficacy. For each patient, they cost US$100,000 per year.

Interferon-gamma is another drug clinically approved for cancer patients, which increases the susceptibility of tumor cells to HER-2 inhibitors. Despite its ability to indirectly increase the death of cancer cells, its use can be limited by side effects.

In the study, the researchers examined the biologic effects of interferon-gamma alone or after anti-erbB2/neu antibody treatment of erbB2-positive cells in mice.

They demonstrated that interferon-gamma alone had no effect on tumors, however trastuzumab or lapatanib administration followed by interferon-gamma significantly inhibited tumor growth and reduce tumor size.

The tumors also became highly sensitive to chemotherapy. This means that drug toxicity could be reduced because the dose of monoclonal antibodies could theoretically be decreased by two-thirds and the amount of chemotherapy by at least half.

Mark Greene, senior author and the John W. Eckman Professor of Medical Science, commented on the potential consequences of these findings: “Individuals previously not able to afford targeted therapy will be able to do so. All of the therapeutic agents used in this preclinical study are approved and we expect to try ordered therapy plus interferon in clinical trials soon.”

Sources: Nagai Y, Tsuchiya H, Runkle EA et al. Disabling of the erbB pathway followed by IFN-γ modifies phenotype and enhances genotoxic eradication of breast tumors. Cell Reports DOI: 10.1016/j.celrep.2015.08.044 (2015); University of Pennsylvania press release