New target for treating wide spectrum of cancers
(Medical Xpress)—UC Irvine biologists, chemists and computer scientists have identified an elusive pocket on the surface of the p53 protein that can be targeted by cancer-fighting drugs. The finding heralds a new treatment approach, as mutant forms of this protein are implicated in nearly 40 percent of diagnosed cases of cancer, which kills more than half a million Americans each year.
In a study published online this week in Nature Communications, the UC Irvine researchers describe how they employed a computational method to capture the various shapes of the p53 protein. In its regular form, p53 helps repair damaged DNA in cells or triggers cell death if the damage is too great; it has been called the "guardian of the genome."
Mutant p53, however, does not function properly, allowing the cancer cells it normally would target to slip through control mechanisms and proliferate. For this reason, the protein is a key target of research on cancer therapeutics.
Within cells, p53 proteins undulate constantly, much like a seaweed bed in the ocean, making binding sites for potential drug compounds difficult to locate. But through a computational method called molecular dynamics, the UC Irvine team created a computer simulation of these physical movements and identified an elusive binding pocket that's open only 5 percent of the time.
After using a computer to screen a library of 2,298 small molecules, the researchers selected the 45 most promising to undergo biological assays. Among these 45 compounds, they found one, called stictic acid, that fits into the protein pocket and triggers tumor-suppressing abilities in mutant p53s.
While stictic acid cannot be developed into a viable drug, noted study co-leader Peter Kaiser, professor of biological chemistry, the work suggests that a comprehensive screening of small molecules with similar traits may uncover a usable compound that binds to this specific p53 pocket.
"The discovery and pharmaceutical development of such a compound could have a profound impact on cancer treatments," Kaiser said. "Instead of focusing on a specific form of the disease, oncologists could treat a wide spectrum of cancers, including those of the lung and breast." He added that there is currently one group of experimental drugs—called Nutlins—that stop p53 degradation, but they don't target protein mutations as would a drug binding to the newly discovered pocket.
The results are the culmination of years of labor by researchers with UC Irvine's Institute for Genomics & Bioinformatics and the Chao Family Comprehensive Cancer Center.
"It's been a large and complex multidisciplinary effort," said Richard Lathrop, professor of computer science and co-leader of the study. "We're working on the leading edge of what's possible, and a variety of skills and expertise is required to make progress. Hopefully, our research eventually will lead to drugs that target many different forms of cancer."
Hartmut Luecke, UC Irvine professor of molecular biology & biochemistry and physiology & biophysics, and Rommie Amaro, an assistant professor of computer science and pharmaceutical sciences who is now at UC San Diego, were other study co-leaders.
Journal reference: Nature Communications
Provided by University of California, Irvine
- Drug kills cancer cells by restoring faulty tumor suppressor May 14, 2012 | not rated yet | 0
- New drug shrinks cancer in animals, study shows Apr 06, 2011 | not rated yet | 0
- Cancer is a p53 protein aggregation disease Mar 29, 2011 | not rated yet | 0
- Cancer biology: Keeping bad company Jan 16, 2013 | not rated yet | 0
- Chemopreventive isothiocyanates selectively depletes mutant p53 in tumor cells Apr 20, 2009 | 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
23 hours ago 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 1 hour ago | not rated yet | 0
Research presented at Digestive Disease Week (DDW) explores new methods for managing digestive health through diet and lifestyle.
Cancer 1 hour ago | not rated yet | 0
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 16 hours ago | 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 |
Patients with treatment-resistant major depression saw dramatic improvement in their illness after treatment with ketamine, an anesthetic, according to the largest ketamine clinical trial to-date led by researchers from the ...
1 hour ago | 4.5 / 5 (2) | 0 |
Regular consumption of coffee is associated with a reduced risk of primary sclerosing cholangitis (PSC), an autoimmune liver disease, Mayo Clinic research shows. The findings were being presented at the Digestive Disease ...
2 hours ago | not rated yet | 0 |
There are significant cost and risk factors associated with two procedures commonly used to diagnose or treat gastrointestinal problems, according to research presented at Digestive Disease Week (DDW).
1 hour ago | not rated yet | 0
An increasing number of U.S. children are experiencing gastrointestinal issues that require interventions to resolve, according to research presented at Digestive Disease Week (DDW).
16 hours ago | not rated yet | 0 |
The latest makeover to a massive psychiatric tome honored by some, reviled by others and even called the "Bible" of mental disorders is being released Saturday with a host of new changes.
14 hours ago | not rated yet | 0
A new case of the deadly coronavirus has been detected in Saudi Arabia where 15 people have already died after contracting it, the health ministry announced on Saturday on its Internet website.
14 hours ago | not rated yet | 0