Triple-negative breast cancer, which is a particularly aggressive and difficult-to-treat form, earns its name because, unlike other breast cancer subtypes, its cells test negative for estrogen and progesterone receptors, as well as for a gene called HER2. Therefore, it cannot respond to therapies that inhibit cancer-growing signals that come from estrogen, progesterone and HER2.
Triple-negative breast cancer is also highly variable from patient to patient and even among tumour cells of a single patient, making it difficult to understand and treat. Other breast cancer subtypes are homogeneous, more predictable and treatable.
The University of Virginia researchers are working to study this variability and find an end-around method to stop triple-negative breast cancer, by seeking out unknown or little-understood routes toward shutting down uncoordinated growth.
"We're interested in the variability that's characteristic of triple-negative breast cancer," said corresponding author Kevin Janes. "We believe this variability gives clues to how the cancer arises, and clues to treatment possibilities that would exploit the way the tumors are regulated or misregulated as the cells communicate with each other.
"Instead of trying to find and target hormones or genes that might promote growth of these tumor cells, as has been successful for other cancer types, we are focusing on a protein in triple-negative tumor cells that normally should inhibit abnormal cell growth, but has been disengaged," Janes said.
Janes and his colleagues have found that GDF11 does not mature properly into a bioactive tumor suppressor, as it should normally do, but instead accumulates within cells in a "pre-active" state.
"This is an exciting realization," Janes said, "because we now can look for ways to remobilize the GDF11 precursor and reengage its normal tumor suppressive activity wherever triple-negative cancer cells reside in the body.
"We're still early in this investigation, but it may be a step in the right direction for getting a handle on ways to target this very difficult to treat breast cancer subtype."
The results are published this week in the journal Developmental Cell. (ANI)