Tumor Cells More Effectively Killed With New Platinum Drug
A new experimental drug based on platinum, called phenanthriplatin, is being tested by researchers at Massachusettes Institute of Technology. The researchers claim this drug kills cancer cells more effectively than cisplatin, the most commonly approved platinum chemotherapy drug.
Platinum-based chemotherapy drugs are among the most powerful and widely used against cancer. However, they do present toxic side effects, and tumor cells can develop a resistance to them. Cisplatin was first approved in the US in 1978 and is most effective in the treatment of testicular cancer but is used in treating many other forms of cancer. Senior author of the study, Stephen Lippard, suggests that phenanthriplatin not only kills cancer cells better than cisplatin, it may also evade cancer-cell resistance to conventional platinum-based drugs.
A major reason that phenanthriplatin appears to be more effective than cisplatin is that it can penetrate cancer cells with greater ease. The second reason is that it blocks transcription – the first step of gene expression, where DNA is converted to RNA.
Platinum-based drugs are effective against cancer because at their center is a platinum atom connected to two ammonion molecules and two chloride ions. The compound has a negative charge, but when it enters the cancer cell it shifts to a positive charge because the chloride ions are replaced by water molecules.
The water molecules are easily displaced, allowing the platinum-based compound to attach to DNA in the cancer cell. The result is cross-links in the DNA that block the cell’s ability to read the code, which is critical for cell function. If enough of the DNA is unreadable, the cell dies. This is how cisplatin works.
In tests using 60 types of cancer cells, phenanthriplatin was between 4 and 40 times more potent than cisplatin, depending on the cancer type. Since this new drug has a different pattern of activity, the researchers suggest it could be effective against cancer types that cisplatin is no good for
When faced with cisplatin, some cancer cells are able to set up defenses that develop resistance to the drug. The cells contain sulfur compounds that are able to attack the platinum and destroy it before it can bind to the DNA. The researchers found phenanthriplitin to evade these defenses because its bulky three-ring attachment seems to block the sulfur from mounting such an effective attack on the platinum.
Lippard and colleagues are now conducting animal tests to determine how the drug spreads in the body and how well it kills tumors in the body as opposed to cells in a test tube. Lippard believes they can further modify the compound to improve its properties.
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