A study recently published in the Proceedings of the National Academy of Sciences describes how to switch these receptor-negative cells back to a state that can be targeted by existing hormone therapies.
“We found that these estrogen-receptor negative cells express high levels of a Notch receptor protein,” says James Haughian, PhD, investigator at the University of Colorado Cancer Center and instructor at the University of Colorado School of Medicine. “And when you blockade this Notch activity, you end up with a pure population of hormone-receptor positive cells.”
Very basically, within a breast cancer, you frequently have different kinds of cells living together – some that have estrogen receptors and thus need to “grab” estrogen in order to survive, grow and replicate. And, Haughian finds, some with similar Notch receptors that need to “grab” Notch proteins in order to survive, grow and replicate. On cells without estrogen receptors but with Notch receptors, they blockade this Notch pathway and the cell again becomes dependent on estrogen – and thus likely treatable with anti-estrogen therapies.
“It’s rare to get something that works so fantastically well as this,” Haughian says.
Whether this switch from hormone-insensitive to hormone-sensitive is due to basic evolution – killing the triple-negative cells leaves more resources for the growth of hormone-receptor positive cells – or whether inhibiting Notch signaling, in fact, causes triple-negative cells to grow hormone receptors is still under investigation.
Whatever the precise mechanism, drugs that inhibit this Notch activity are already in clinical trials for breast cancer. However, Kathryn Horwitz, PhD, investigator at the CU Cancer Center and Distinguished Professor of Endocrinology at the CU School of Medicine theorizes that, “Monotherapy with a Notch inhibitor might not be enough on its own, but may convert the cancer into a hormone-therapy treatable state.”
This finding that Notch inhibition converts a triple-negative cancer subpopulation to a hormone-receptor positive population implies the potential usefulness of combination therapy – perhaps a Notch inhibitor to make all the cancer’s cells hormone-sensitive, followed by an anti-estrogen to treat them.
“Theorizing that and proving it is another matter,” Horwitz says. “But if a clinician came knocking on our door, we’d say hey, let’s try it.”
Research funded by the National Institutes of Health (NIH), the Breast Cancer Research Foundation and the Avon Foundation for Women
Garth Sundem | EurekAlert!
Chip-based optical sensor detects cancer biomarker in urine
06.12.2019 | The Optical Society
Scientist identify new marker for insecticide resistance in malaria mosquitoes
06.12.2019 | Liverpool School of Tropical Medicine
University of Texas and MIT researchers create virtual UAVs that can predict vehicle health, enable autonomous decision-making
In the not too distant future, we can expect to see our skies filled with unmanned aerial vehicles (UAVs) delivering packages, maybe even people, from location...
With ultracold chemistry, researchers get a first look at exactly what happens during a chemical reaction
The coldest chemical reaction in the known universe took place in what appears to be a chaotic mess of lasers. The appearance deceives: Deep within that...
Abnormal scarring is a serious threat resulting in non-healing chronic wounds or fibrosis. Scars form when fibroblasts, a type of cell of connective tissue, reach wounded skin and deposit plugs of extracellular matrix. Until today, the question about the exact anatomical origin of these fibroblasts has not been answered. In order to find potential ways of influencing the scarring process, the team of Dr. Yuval Rinkevich, Group Leader for Regenerative Biology at the Institute of Lung Biology and Disease at Helmholtz Zentrum München, aimed to finally find an answer. As it was already known that all scars derive from a fibroblast lineage expressing the Engrailed-1 gene - a lineage not only present in skin, but also in fascia - the researchers intentionally tried to understand whether or not fascia might be the origin of fibroblasts.
Fibroblasts kit - ready to heal wounds
Research from a leading international expert on the health of the Great Lakes suggests that the growing intensity and scale of pollution from plastics poses serious risks to human health and will continue to have profound consequences on the ecosystem.
In an article published this month in the Journal of Waste Resources and Recycling, Gail Krantzberg, a professor in the Booth School of Engineering Practice...
03.12.2019 | Event News
15.11.2019 | Event News
15.11.2019 | Event News
06.12.2019 | Earth Sciences
06.12.2019 | Life Sciences
06.12.2019 | Information Technology