Novel technique switches triple-negative breast cancer cells to hormone-receptor positive cells
Within many hormone-receptor positive breast cancers lives a subpopulation of receptor-negative cells knock down the hormone-receptor positive cells with anti-estrogen drugs and you may inadvertently promote tumor takeover by more dangerous, receptor-negative cells. 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 so 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 these cells without estrogen receptors but with Notch receptors, 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 University of Colorado 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."
Provided by University of Colorado Denver
- Study finds new points of attack on breast cancers not fueled by estrogen Jul 11, 2011 | not rated yet | 0
- Childbearing may increase risk of hormone receptor-negative breast cancer in African-American women Aug 16, 2011 | not rated yet | 0
- New biomarker predicts effectiveness of breast cancer drugs Dec 07, 2006 | not rated yet | 0
- Key growth factor identified in T cell leukemia Aug 01, 2011 | not rated yet | 0
- Protein that fuels lethal breast cancer growth emerges as potential new drug target Oct 17, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
In recent years, microRNAs (miRNAs) and other non-coding RNAs are small molecules that help control the expression of specific proteins. In recent years they have emerged as disease biomarkers. miRNA profiles have been used ...
Cancer 18 hours ago | not rated yet | 0
Cancer cells spread and grow by avoiding detection and destruction by the immune system. Stimulation of the immune system can help to eliminate cancer cells; however, there are many factors that cause the immune system to ...
Cancer 18 hours ago | 5 / 5 (1) | 0
Researchers from London's Kingston University have begun a two-year study which could help prolong the lives of people with colorectal tumours.
Cancer 21 hours ago | 5 / 5 (1) | 0
Transformative research from Western University has identified new hormones in the body which may suppress breast cancer and stimulate the regression of breast tumors.
Cancer 22 hours ago | 5 / 5 (2) | 0
(Medical Xpress)—Curtin University researchers have found evidence that targeting specific cells in the body can reverse the effects of cancer on the immune system.
Cancer 22 hours ago | 5 / 5 (4) | 0
Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...
5 minutes ago | not rated yet | 0
Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...
10 minutes ago | not rated yet | 0
Mortality and length of stay are highest in heart failure patients admitted in January, on Friday, and overnight, according to research presented today at the Heart Failure Congress 2013. The analysis of nearly 1 million ...
6 minutes ago | not rated yet | 0
(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...
21 hours ago | 5 / 5 (3) | 0 |
Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...
16 hours ago | 3 / 5 (2) | 0 |
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
18 hours ago | 3.7 / 5 (3) | 0 |