PTK6 blocker could treat or even prevent ER+ breast cancer metastasis

Researchers from the Icahn School of Medicine have pinpointed an enzyme, PTK6, which could be targeted to quash the growth of estrogen receptor-positive (ER+) breast cancer, a common form of the disease.

Approximately 65% of breast cancers express either the estrogen receptor (ER+) or the progesterone receptor (PR+), the researchers said. The enzyme PTK6, or tyrosine kinase 6, is abundant in several tumor types, including prostate, ovarian and breast cancers, and can foster the growth, survival and migration of ER+ breast cancer cells.

The standard treatments for ER+ breast cancer are endocrine therapies, such as tamoxifen and aromatase inhibitors. But these drugs are not effective in all patients. An alternative treatment would provide relief for the subset of patients whose disease is drug-resistant.

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"Endocrine therapies are still the most effective medical therapy for this subtype of breast cancer, and the end goal is to inhibit growth and/or kill ER+ breast cancer cells," said senior author Hanna Irie, M.D. "However, some breast cancer patients still develop metastatic ER+ disease despite these common endocrine therapies, so newer treatments are very important and necessary to kill endocrine therapy-resistant cancers."

The researchers found that inhibiting PTK6 in ER+ breast cancer cells, including those resistant to tamoxifen and estrogen deprivation, triggers apoptosis—or programmed cell death. The findings appear in NPJ Breast Cancer.

“We are excited and gratified by these remarkable results, which could lead to a new way to treat these drug-resistant metastases of ER+ breast cancers and/or prevent their metastases in the first place,” said Irie, an assistant professor of medicine (hematology and medical oncology) and oncological sciences at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai.

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Breast cancer is the second-leading cause of cancer death in women, aside from skin cancer. In 2017 alone, more than 252,000 women will have been diagnosed with breast cancer and more than 40,000 will die from it, the American Cancer Society estimates.

Several companies have made strides in the breast cancer space this year—Eli Lilly grabbed an FDA nod in September for Verzenio, a drug for the HR-positive, HER2-negative form of the disease, while Puma scored approval in July for its HER2-positive med, Nerlynx.

It hasn’t been smooth sailing for everyone though. Pfizer and Astellas recently called it quits trying to expand Xtandi into breast cancer. Picked up in Pfizer’s $14 billion acquisition of Medivation, the drug is already FDA-approved for the treatment of prostate cancer.