Corporate Banner
Satellite Banner
ADME Tox
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

New Drug Candidate Shows Promise Against Cancer

Published: Wednesday, July 11, 2012
Last Updated: Wednesday, July 11, 2012
Bookmark and Share
Drugs containing platinum are among the most powerful and widely used cancer drugs. However, such drugs have toxic side effects, and cancer cells can eventually become resistant to them.

MIT chemistry professor Stephen J. Lippard, who has spent much of his career studying platinum drugs, has now identified a compound that kills cancer cells better than cisplatin, the most commonly used platinum anticancer drug. The new compound may be able to evade cancer-cell resistance to conventional platinum compounds.

“I’ve long believed that there’s something special about platinum and its ability to treat cancer,” Lippard says. Using new variants, “we might have a chance of applying platinum to a broader range of cancer types, more successfully,” he says.
Lippard is senior author of a paper describing the new drug candidate, known as phenanthriplatin, in the Proceedings of the National Academy of Sciences (PNAS). Lead author is postdoc Ga Young Park; other authors are graduate student Justin Wilson and postdoc Ying Song.

Cisplatin, first approved to treat cancer in 1978, is particularly effective against testicular cancer, and is also used to treat ovarian and some lung tumors, as well as lymphoma and other cancers. At its center is a platinum atom bound to two ammonia molecules and two chloride ions. When the compound enters a cancerous cell, it becomes positively charged because water molecules replace its chloride ions. The resulting positive ion can attack negatively charged DNA, forming cross-links with the DNA strands and making it difficult, if not impossible, for the cell to read that section of DNA. Too much of this damage, if not repaired, kills the cell.

For many years, Lippard has studied the mechanism of cisplatin’s action and has pursued similar drugs that could be more powerful, work against more types of cancer, have fewer side effects and evade cancer-cell resistance.

One way to do that is to vary the structure of the platinum compound, altering its activity. In this case, the researchers studied compounds that are similar to cisplatin, but have only one replaceable chlorine atom. Such a compound can bind to DNA at only one site instead of two.

From early research on platinum compounds done in the 1970s, researchers thought that platinum compounds needed two DNA binding sites to have an effect on cancer cells. However, in the 1980s, it was discovered that certain positively charged platinum compounds that can only bind to DNA at one site have anti-cancer activity, rekindling interest in them.

In 2008, Lippard’s group investigated a compound called pyriplatin, in which one of the chlorine atoms of cisplatin is replaced by a six-membered pyridine ring that includes five carbon atoms and one nitrogen atom. This compound had some anti-cancer activity, but was not as powerful as cisplatin or oxaliplatin, another FDA-approved platinum-based cancer drug.

Lippard then set out to create similar compounds with larger rings, which he theorized might be more effective at blocking DNA transcription. One of those was phenanthriplatin, the compound described in the new PNAS paper.

Phenanthriplatin was tested against 60 types of cancer cells as part of the National Cancer Institute’s cancer-drug screening program, and it was found to be four to 40 times more potent than cisplatin, depending on the cancer type. It also showed a different pattern of activity than that of cisplatin, suggesting that it could be used to treat types of cancer against which cisplatin is ineffective.

One reason for the efficacy of phenanthriplatin is that it can get into cancer cells more easily than cisplatin, Lippard says. Previous studies have shown that platinum compounds containing carbon can pass through specific channels, found in abundance on cancer cells, that allow positively charged organic compounds to enter. Another reason is the ability of phenanthriplatin to inhibit transcription, the process by which cells convert DNA to RNA in the first step of gene expression.

Another advantage of phenanthriplatin is that it seems to be able to evade some of cancer cells’ defenses against cisplatin. Sulfur-containing compounds found in cells, such as glutathione, can attack platinum and destroy it before it can reach and bind to DNA. However, phenanthriplatin contains a bulky three-ring attachment that appears to prevent sulfur from inactivating the platinum compounds as effectively.

Luigi Marzilli, a professor of chemistry at Louisiana State University, says the new compound appears to be very promising. “It expands the utility of platinum drugs and avoids some of the problems that existing drugs have,” says Marzilli, who was not part of the research team.

The researchers are now conducting animal tests to determine how the drug is distributed throughout the body, and how well it kills tumors. Depending on the results, they may be able to modify the compound to improve those properties, Lippard says.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Microscopic “Walkers” Find Their Way Across Cell Surfaces
Technology could provide a way to deliver probes or drugs to cell structures without outside guidance.
Thursday, October 23, 2014
Getting Metabolism Right
Analysis of 89 models of metabolic processes finds flaws in 44 of them — but suggests corrections.
Thursday, October 09, 2014
DARPA and NIH to Fund ‘Human Body on a Chip’ Research
MIT-led team to receive up to $32 million to develop technology that could accelerate pace and efficiency of pharmaceutical testing.
Wednesday, July 25, 2012
Team Develops Nanoparticles to Battle Cancer
An MIT professor and her colleagues have created nanoparticles that mimic blood platelets.
Monday, February 05, 2007
Scientific News
RNAi Screening Trends
Understand current trends and learn which application areas are expected to gain in popularity over the next few years.
New Material Opens Possibilities for Super-Long-Acting Pills
A pH-responsive polymer gel could create swallow able devices, including capsules for ultra-long drug delivery.
Long-sought Discovery Fills in Missing Details of Cell 'Switchboard'
A biomedical breakthrough reveals never-before-seen details of the human body’s cellular switchboard that regulates sensory and hormonal responses.
Tracking Breast Cancer Before it Grows
A team of scientists led by University of Saskatchewan researcher Saroj Kumar is using cutting-edge Canadian Light Source techniques to screen and treat breast cancer at its earliest changes.
Zebrafish Reveal Drugs that may Improve Bone Marrow Transplant
Compounds boost stem cell engraftment; could allow more matches for patients with cancer and blood diseases.
Teeth Reveal Lifetime Exposures to Metals, Toxins
Researchers have identified dental biomarkers to reveal links between early iron exposure and late life brain diseases.
An Innovative Algorithm to Decipher How Drugs Work Inside the Body
Researchers at Columbia University Medical Center (CUMC) have developed a computer algorithm that is helping scientists see how drugs produce pharmacological effects inside the body.
Uncovering the Spread of Bacteria in Pneumonia
Northwestern Medicine scientists have discovered the role a toxin produced by a pneumonia-causing bacterium plays in the spread of infection from the lungs to the bloodstream in hospitalized patients.
Ferring Bets on Bacteriophages to Treat Inflammatory Bowel Disease
Ferring Pharmaceuticals have annoucned that it will collaborate with Intralytix in the latest phase of its early stage development programme for a bacteriophage-based therapy for inflammatory bowel disease (IBD).
Rare Form: Novel Structures Built from DNA Emerge
DNA, the molecular foundation of life, has new tricks up its sleeve. The four bases from which it is composed can be artificially manipulated to construct endlessly varied forms in two and three dimensions.
SELECTBIO

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!