Melanoma treatment options one step closer
November 2, 2009 - (Edmonton) A targeted chemotherapy for the treatment of skin cancer is one step closer, after a team of University of Alberta researchers successfully synthesized a natural substance that shows exceptional potential to specifically treat this often fatal disease.
U of A chemistry professor Dennis Hall says that, after three years of work, his research team has become just the third lab in the world to successfully synthesize a substance called Palmerolide A.
"The potency of Palmerolide A is exceptional, and melanoma is a very aggressive cancer, for which there is almost no chemotherapeutic recourse," said Hall. "Natural substances like Palmerolide A offer real hope for such treatments."
The molecule Palmerolide A was first isolated in a secretion used by tunicates - otherwise known as sea squirts - as a defense mechanism for life in the frigid deeps surrounding the Antarctic.
"I find it interesting that the molecule has the potential to fight a disease that comes from exposure to the sun, yet it was isolated in the Antarctic Ocean in an area where there is no sun," said Hall. "Unfortunately, you can get only milligrams of the material from each sea squirt.
"If this molecule ever pans out to be a drug, synthetic chemistry will be the only solution, given the supply problem."
While researchers are not exactly clear on how Palmerolide A acts on melanoma, Hall says the discovery has given hope to skin-cancer researchers because current chemotherapy as an overall strategy is not very effective in treating melanoma.
"Melanoma tumors thicker than one millimetre means it has metastasized and that's the stage where there is almost no recourse," said Hall. "One of the problems with most cancer drugs is the lack of selectivity for cancer cells versus normal cells. Preliminary data for Palmerolide A looks very promising in terms of solving this issue."
Hall is quick to point out, however, that this breakthrough is still very much in its infancy. Even before it gets to a form that could be tested, Hall explains the process for synthesizing this molecule - which currently requires a carefully planned sequence of 21 highly controlled chemical reactions - needs to be substantially refined.
"It is a pretty big molecule and a synthesis of 21 steps is too long to be practical," said Hall. "For commercialization, the structure needs to be made more drug-like, smaller and more water-soluble, while preserving the potency of the molecule.
"This whole process will take over 10 years and there's no guarantee of success. That's pretty standard in the drug discovery field - but Palmerolide A would certainly fill a big void if it delivers."
Hall's research findings were recently published in the Journal of the American Chemical Society.
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