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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