Chemo may get boost from cholesterol-related drug
Johns Hopkins investigators are testing a way to use drugs that target a cholesterol pathway to enhance the cancer-killing potential of standard chemotherapy drugs. Their tests, in mouse models of pancreatic cancer, may yield new and more effective combinations of current and possibly new anti-cancer drugs.
Besides their deadly consequences, pancreatic cancer and heart disease share a connection with genetic pathways that control cholesterol and a cell signaling system known as the Hedgehog pathway. (The name refers to the shape of its mutated protein in fruit flies, one that resembles the spiky-haired animal.)
Over-activity in the Hedgehog pathway has long been known to trigger many types of cancer and is the focus of five new drugs currently in development. Each of the drugs targets the same cell-surface protein that forms the business end of the Hedgehog pathway, according to the investigators, but tumors find a way to mutate the protein and make cancer cells resistant to these new therapies.
Looking for another way to target the Hedgehog pathway, investigator William Matsui, M.D., Ph.D., professor at the Johns Hopkins Kimmel Cancer Center, teamed up with UCLA biologist Farhad Parhami, Ph.D, who had studied connections between components of cholesterol and Hedgehog pathways.
Parhami found that derivatives of cholesterol, called oxysterols, regulate the Hedgehog pathway via so-called "liver x receptors," which bind to cholesterol and guide redistribution of cholesterol throughout the body. In doing so, liver x receptors block the Hedgehog pathway.
"Activating liver x receptor could be an alternate target for blocking the Hedgehog pathway," says Matsui, who notes that activating a target to create an anti-tumor effect is an unusual strategy in therapy. Most drugs currently in development aim to block pathways not activate them, he says.
For the Hopkins study, mice bearing implanted human pancreatic tumors received treatments of a drug called TO901317 that activates liver x receptors along with a chemotherapy drug called gemcitabine. If given alone, the liver-x receptor drug did not affect tumor growth, but in combination with gemcitabine, the tumors shrank, and investigators found a five-fold reduction in expression of Hedgehog pathway components.
Matsui says that pancreatic tumors are crowded with scar tissue, and chemotherapy drugs encounter difficulty finding cancer cells amid the scar tissue. Blocking the Hedgehog pathway by activating liver x receptors may help pancreatic cancer drugs penetrate the tumor and attack cancer cells.
Matsui and Parhami, in collaboration with UCLA chemists Michael Jung and Frank Stappenbeck, are currently developing novel, more effective and safer liver X receptor activators for use in targeting pancreatic cancer and other Hedgehog pathway-mediated tumors.
Funding for the study was provided by the National Cancer Institute.
Provided by Johns Hopkins Medical Institutions
- Researchers discover new molecular pathway for targeting cancer, disease Jul 20, 2009 | not rated yet | 0
- NDSU assistant professor publishes paper on pancreatic tumor regulator Feb 17, 2012 | not rated yet | 0
- Treating deadly brain tumors by combining drugs Jan 12, 2011 | not rated yet | 0
- New mechanism of pancreatic cancer discovered May 31, 2010 | not rated yet | 0
- Scientists link two cancer-promoting pathways in esophageal cancer Mar 19, 2012 | 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
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...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
The use of a smartphone application significantly improves patients' preparation for a colonoscopy, according to new research presented today at Digestive Disease Week (DDW). The preparation process, which begins days in ...
Cancer 20 hours ago | not rated yet | 0
Research presented at Digestive Disease Week (DDW) explores new methods for managing digestive health through diet and lifestyle.
Cancer 21 hours ago | not rated yet | 1
A ground-breaking advance in colonoscopy technology signals the future of colorectal care, according to research presented today at Digestive Disease Week(DDW). Additional research focuses on optimizing the minimal withdrawal ...
Cancer May 18, 2013 | 5 / 5 (2) | 0
(HealthDay)—Concurrent use of two immune checkpoint antibodies—ipilimumab and nivolumab—may be effective for the treatment of advanced melanoma, according to a proof-of-principal study presented in ...
Cancer May 17, 2013 | not rated yet | 0
(HealthDay)—The risks of metastasis and death associated with cutaneous squamous cell carcinoma (CSCC) are low, but significant, and risk factors for poor outcome include tumor diameter, invasion beyond ...
Cancer May 17, 2013 | not rated yet | 0 |
Researchers at the University of Wisconsin have identified a potential new risk factor for obstructive sleep apnea: asthma. Using data from the National Institutes of Health (Heart, Lung, and Blood Institute)-funded Wisconsin ...
8 hours ago | not rated yet | 0 |
In their quest to learn more about the variability of cells between and within tissues, biomedical scientists have devised tools capable of simultaneously measuring dozens of characteristics of individual ...
9 hours ago | 5 / 5 (2) | 0 |
Scientists at Johns Hopkins have turned their view of osteoarthritis (OA) inside out. Literally. Instead of seeing the painful degenerative disease as a problem primarily of the cartilage that cushions joints, ...
9 hours ago | 4.8 / 5 (4) | 0 |
A new study looking at sleep-disordered breathing (SDB) and markers for Alzheimer's disease (AD) risk in cerebrospinal fluid (CSF) and neuroimaging adds to the growing body of research linking the two.
8 hours ago | 5 / 5 (2) | 0 |
The hunt for an HIV vaccine has gobbled up $8 billion in the past decade, and the failure of the most recent efficacy trial has delivered yet another setback to 26 years of efforts.
13 hours ago | not rated yet | 0
Gourmands and foodies everywhere have long recognized ginger as a great way to add a little peppery zing to both sweet and savory dishes; now, a study from researchers at Columbia University shows purified components of the ...
8 hours ago | not rated yet | 0