LANL scientist aids hunt for cancer cure

·5 min read

Dec. 6—SANTA FE — A potential melanoma-fighting compound has been discovered in the sea floor near Antarctica by a team that included a scientist from Los Alamos National Laboratory.

In new research published Wednesday in the journal mSphere, Patrick Chain, a senior scientist and Laboratory Fellow at LANL, and researchers from the University of South Florida and the Desert Research Institute, "successfully traced a naturally produced melanoma-fighting compound called 'palmerolide A' to its source: a microbe" that lives in an underwater species called an ascidian, known as a "sea squirt." The species is common to the Antarctic waters of the Anvers Island archipelago, LANL said in a news release.

"Palmerolide A" is a toxin that can specifically damage melanoma cells.

Chain, 48, is with the Bioscience Division at LANL. He did not go to Antarctica for the research but hopes to join a future exploration.

A sea squirt is an invertebrate marine animal shaped like a potato that is primarily sessile, meaning it is permanently fixed to a surface.

"There are few places farther from your medicine cabinet than the tissues of an ascidian, or 'sea squirt,' on the icy Antarctic sea floor — but this is precisely where scientists are looking to find a new treatment for melanoma, one of the most dangerous types of skin cancer," the mSphere journal article said.

The research, conducted several years ago, produced several important findings, Chain said.

"Perhaps the most relevant to the public is that we have tracked down and done a lot of detective work to figure out which organisms and the underlying molecular machines that are making potential anti-melanoma properties," Chain said.

The "palmerolide A" chemical was discovered by one of the study's co-authors "to have very selective cytotoxicty (the degree a substance can damage a cell) towards melanoma so it kills specifically melanoma cells and because it's so specific ... is viewed as very promising as a cancer therapeutic," Chain said.

"Melanoma is one of the worst skin cancers," he added.

"That is the hope — that this would be a treatment not toxic to you but toxic to the cells, the melanoma cells, so it could be a treatment for that specific cancer," said Chain, when asked if this could be a cure for melanoma.

According to the American Cancer Society website, "cancer of the skin is by far the most common of all cancers" and although melanoma "accounts for only about 1% of skin cancers ... (it) causes a large majority of skin cancer deaths."

The Cancer Society estimates about 106,110 new melanomas will be diagnosed in 2021 with about 7,180 deaths.

Undiscovered bacterium

The sea squirts at the bottom of the Antarctic "just like all other organisms that we've explored have their own microbiota (ecological communities of microorganisms)," Chain said. "And we've discovered that the organism really responsible for creating this potential drug is actually a very poorly characterized and previously undiscovered bacterium that resides inside these sea squirts."

There are many undersea explorations in the oceans "to find as much biodiversity as possible and kind of grind them up and look for chemicals that might have potency either as antibiotics ... or as anti-cancer therapeutics," according to Chain.

The genes responsible for making the anti-melanoma compound "it turns out that these genes actually reside in the genome or in the cells of some bacteria that are tightly coupled to the sea squirt," Chain said.

The bacteria the team of scientists discovered is unique to the potato-shaped sea squirts.

"We don't see them (the bacteria) in the surrounding waters we only see them in the sea squirt," Chain said.

"This type of sea squirt species is prevalent in a very thin slice, depth profile wise of this area of the Antarctic," Chain said.

"Throughout the course of disentangling the many genomic fragments of the various species in the microbiome (microorganisms in a particular environment), we discovered that this novel microbe's genome appears to harbor multiple copies of the genes responsible for palmerolide production," said Chain, in the article.

Alison Murray, the article's lead author and a research professor at the Desert Research Institute, wrote, "We have long suspected that palmerolide A was produced by one of the many types of bacteria that live within" the sea squirt.

"Now, we have actually been able to identify the specific microbe that produces this compound, which is a huge step forward toward developing a naturally derived treatment for melanoma," Murray wrote.

Future steps are to "better understand and characterize how this chemical is made" and we have a study expected to be published in the coming weeks in another journal "that describes the biochemical pathways to create this product," Chain said.

Now scientists hope to find out if they can create the anti-melanoma bacteria in mass quantities.

"The next step really is now that we understand how it's being made and what genes are responsible can we actually take those genes and either put it in a surrogate host or do something outside of the host in vitro (in a test tube) to create this product in mass quantities," according to Chain.

Scientists hope to isolate the bacteria and use CRISPR, a technology for editing genomes, or a complete set of genetic material in a cell, to further their research. This technology for editing genomes is used for treating and preventing spread of diseases.

Chain said that producing a drug from the bacteria is exactly how penicillin was discovered. "It's likely a five-year time frame" before an anti-melanoma drug could potentially be produced, Chain said.

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