Approved Therapy, Ibrance, Seen to Block Metastasis in Triple Negative Breast Cancer Study

Approved Therapy, Ibrance, Seen to Block Metastasis in Triple Negative Breast Cancer Study

Researchers may be one step closer to preventing triple-negative breast cancer, the most aggressive subtype of breast cancer, from spreading elsewhere in a person.

Ibrance (palbociclib), an FDA-approved drug for estrogen receptor-positive breast cancer, could also effectively block metastasis in triple-negative breast cancers, they report. The drug, however, did not affect growth in the original tumor.

The study, “CDK4/6-dependent activation of DUB3 regulates cancer metastasis through SNAIL1,” was published in Nature Communications.

“Metastasis is a hallmark of cancer and a leading cause of cancer death,” Zhenkun Lou, PhD, of Mayo Clinic, the study’s senior author, said in a press release. “Despite great progress in cancer therapy, the prevention of cancer metastasis is still an unfulfilled challenge.”

Lou and his team had a hint that inhibiting CDK4/6, which regulates a cancer metastasis protein, could influence the transition of immotile cancer cells into migratory cells — a process called epithelial-to-mesenchymal transition (EMT).

They focused particularly on triple-negative breast cancer cells because such cancers are known to grow the fastest and to be more metastatic than any other breast cancer subtype.

“Prior published data suggested that CDK 4/6 inhibitors were not effective in reducing the growth rates of estrogen receptor negative breast cancer,” said Lou. “Our data confirmed that, while the rate of growth of triple-negative breast cancer was not affected by CDK 4/6 inhibitors, this class of drugs was able to significantly inhibit the spread of triple-negative breast cancer to distant organs when tested in multiple different triple-negative breast cancer models.”

This was true not only in triple-negative breast cancer cells cultured in the lab, but also in several breast cancer mouse models, including mice implanted with tumors isolated from triple-negative cancer patients.

Further work explored the mechanism through Ibrance, a CDK4/6 inhibitor, prevented these breast tumors from spreading. They found that CDK4/6 activity was required to stabilize a protein, called SNAIL, involved in the transition to migratory cells. Without SNAIL, the cells could no longer undergo the transformation that allowed them to spread.

“These findings may provide a new treatment for the prevention of cancer metastasis,” said a study co-author, Matthew Goetz, MD, an oncologist and co-leader of the Women’s Cancer Program at Mayo Clinic. “Mayo Clinic is now developing new studies that will focus on the role of CDK 4/6 inhibitors and their potential to inhibit cancer metastasis in women with triple-negative breast cancer who are at highest risk for cancer metastasis.”

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