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!
Magic number colloidal clusters
13.12.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
Record levels of mercury released by thawing permafrost in Canadian Arctic
13.12.2018 | University of Alberta
What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...
What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.
Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
13.12.2018 | Life Sciences
13.12.2018 | Physics and Astronomy
13.12.2018 | Earth Sciences