How snake venom could help fight cancer

Generally, most of us try to get through life without having to cross paths with a venomous animal. But the dangerous substances in a snake's bite or a scorpion's sting may actually have value: In recent years, scientists have begun to investigate the disease-fighting properties of venom.

"Cancer [treatment] is an emerging area in venom research," says Mandë Holford, a biochemist at the City University of New York's Hunter College. Her research subjects are venomous marine snails, which she describes as "walking drug factories," due to the useful medicinal compounds in their venom.

There's a growing body of research examining the chemicals in various animal and plant toxins and their potential effectiveness in treating conditions from chronic pain to HIV. Experiments show that some of these substances have a curious ability to bind selectively to cancer cells and inhibit their growth. Among the toxic molecules that could treat cancer are melittin, a peptide in bee venom, and contortrostatin, a protein in copperhead snake venom. Although experts can't fully explain exactly how the toxins bind to cancer cells, this quality makes them ideal for treating cancer.

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Using venom to treat cancer is not a totally new idea; one cancer therapy method in traditional Chinese medicine, known as huachansu, uses the venom secreted from a Bufo toad's skin glands and has been around for 1,000 years (though the scientific proof to back this therapy has been muddy at best.) Further evidence of venom's promise in cancer research came from the Fred Hutchinson Cancer Center in Seattle, where James Olson and his colleagues found that chlorotoxin from the Israeli yellow scorpion could bind to tumor cells and help neurosurgeons highlight the boundaries of brain cancer during the operation. Since this discovery in 2007, eventually dubbed "tumor paint," Olson's laboratory has been devoted to looking at venom for sources of potential cancer drugs and has zeroed in on a class of proteins with knotted structures — called, appropriately enough, knottins.

"They're tough little proteins, not like any I've ever dealt with in previous research, and they're often found in venom," says Chris Mehlin, who leads the peptide drug discovery initiative at the Fred Hutchinson Cancer Center. "Our laboratory is focused on knottins because they're full of functions that can affect cancer cells."

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Using venom to treat cancer is not as simple as injecting these proteins into a patient, which could actually be quite dangerous. A courier is needed to deliver the protein right to the cancer cells. Dipanjan Pan, an assistant professor in bioengineering at the University of Illinois at Urbana-Champaign, leads one of several labs that are exploring the use of nanotechnology to point the venom-derived proteins toward the right target. Pan injects dense amounts of synthesized proteins — modeled after ones found in bee and scorpion venom — into plastic nanoparticles, and applies these nanoparticles to breast cancer and melanoma cells in the laboratory. Holford compares this sneaky nanotechnological method of delivery to the classic Trojan horse: In this case, the body's immune system has to be fooled into letting the package in through its defenses.

"Our data shows that using nanoparticles to deliver these peptides is safe, as they don't induce an immune response," says Pan, who presented his research at a recent American Chemical Society conference.

The ability of venom-based therapy to avoid damaging healthy cells gives it an advantage over more conventional treatments for cancer, such as chemotherapy. In addition to attacking rapidly dividing tumor cells, chemotherapeutic drugs can destroy fast-growing normal cells, such as those in hair and mucous membranes along the mouth and throat, leading to unpleasant side effects. Mehlin proposes that drugs developed from these venom-based proteins would be small enough to target protein-to-protein interactions involved in a cancer's growth.

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Since there's been limited testing of venom-based therapies in animal models, let alone in humans, it could be a while before cancer drugs made from venom become available. But researchers like Pan look forward to testing these drugs on animal subjects in the near future. The desert-wandering Israelites in the Old Testament looked upon a bronze snake to be healed, and modern patients may one day owe thanks to the real thing.