Breast cancer: Discovery of new factor may improve therapy

The Centers for Disease Control and Prevention (CDC) estimate that around 237,000 women and 2,100 men are diagnosed with breast cancer every year in the United States.

Some of the main risk factors for breast cancer include age, breast density, and whether there is a family history of the condition.

At the moment, breast cancer is treated using chemotherapy, hormonal therapy, radiation therapy, or surgery when needed.

However, researchers are constantly on the lookout for new therapeutic targets; they are hoping to develop more effective treatments.

Recently, Dr. Charles Clevenger and team, at Virginia Commonwealth University’s Massey Cancer Center in Richmond, found that an enzyme that is ultimately involved in the production of breast milk may also play a role in the development of breast cancer.

The researchers report their discovery in a paper now published in the journal Cancer Research.

Removing one enzyme slows down cancer

Dr. Clevenger and colleagues first observed that an enzyme called cyclophilin A (CypA) controls a genetic pathway known as Jak2/Stat5, which plays a key role in the development of mammary glands, which are the milk-expressing glands in the breasts.

However, Jak2/Stat5 signaling is also involved in the growth of breast cancer tumors.

When the researchers tried deleting CypA in mouse models with estrogen receptor-positive breast cancer and estrogen receptor-negative breast cancer, it inhibited the carcinogenic activity of Stat5 signaling.

By doing this, the scientists slowed down — and, in some cases, even stopped — the growth of breast cancer cells in the rodents.

“This research identifies [CypA] as a relevant target for therapeutic intervention in breast cancer,” explains Dr. Clevenger.

He goes on, “Because [Food and Drug Administration]-approved drugs are available to inhibit the action of CypA, translation of these findings to breast cancer patients should be rapid.”

The researchers were clued in on the potential importance of CypA in breast cancer by previous studies that Dr. Clevenger conducted, which looked at the signaling pathways for prolactin (PRL), which is a hormone that stimulates the production of breast milk.

In his previous research, Dr. Clevenger showed that PRL receptor (PRLr) signaling plays a role in the growth of breast cancer tumors.

Furthermore, when he looked at the genetic pathways linked to PRLr signaling — which include Jak2/Stat5 — he also found that CypA played an important role in activating these pathways.

Unimpaired lactation in mouse models

In the current study, the researchers also found that even when they removed CypA from the mice, it did not affect their ability to express milk.

“This study demonstrated many similarities to other loss-of-function mouse models of the PRL-PRLr-Jak2/Stat5 signaling pathway,” Dr. Clevenger notes.

“However, what distinguishes the CypA-deprived mouse models from the other genetic deletion models was the mice’s ability to still successfully lactate and nurse their offspring, despite the loss of an enzyme critical to mammary gland development.”

Dr. Charles Clevenger

According to the team, this suggests that, while Jak2/Stat5 signaling may have been significantly weakened by CypA deletion, it might not have been fully deactivated.

This is the first time that a study has explored the role of this key enzyme in the development of breast cancer, and the scientists are hopeful that their discovery may lead to more targeted therapies.

“No study to date had previously examined the loss of CypA function during mammary development and the formation of cancer,” says Dr. Clevenger.

Source: Read Full Article