A study by researchers at the Ohio State University Comprehensive Cancer Center—Arthur G. James Cancer Hospital and Richard J. Solove Research Institute has discovered how tamoxifen-resistant breast cancer cells grow and proliferate. It also suggests that an experimental agent might offer a novel targeted therapy for tamoxifen-resistant breast cancer. Like a second door that opens after the first door closes, a signaling pathway called hedgehog (Hhg) can promote the growth of breast cancer cells after tamoxifen shuts down the pathway activated by the hormone estrogen. A second signaling pathway, called PI3K/AKT, is also involved.
Activation of the Hhg pathway renders tamoxifen treatment ineffective and enables the tumor to resume its growth and progression. As part of the study, published in the journal Cancer Research, the researchers analyzed over 300 human tumors and found that those with an activated Hhg pathway had a worse prognosis. Finally, the researchers showed that an experimental drug called vismodegib, which blocks the Hhg pathway, inhibits the growth of tamoxifen-resistant human breast tumors in an animal model. Vismodegib is in clinical trials testing for other types of cancer.
Currently, chemotherapy is used to treat hormone-resistant breast cancers, but this is associated with significant side effects. This study has identified targeted therapies that could be an alternative to chemotherapy for these resistant tumors. “Our findings suggest that we can target this pathway in patients with estrogen-receptor breast cancers who have failed tamoxifen therapy,” says first author Bhuvaneswari Ramaswamy, MD, a medical oncologist specializing in breast cancer. Read an abstract of the study.