One day cancer may
be regarded as a
chronic condition to be
managed over a lifetime
A Pill a Day to Keep Cancer Away?
September 23, 2009
by Brendon Nafziger
, DOTmed News Associate Editor
Safe drugs that starve growing tumors of blood could turn cancer into a "chronically manageable disease," according to researchers in Israel.
Ronit Satchi-Fainaro, Ph.D., a researcher in nanotechnology at Tel Aviv University, and her team were able to shrink tumors in mice by more than 50 percent by cutting off the tumors' blood supply, according to two papers published recently in PLoS One and the German chemistry journal Angewandte Chemie.
Even more importantly, their therapy appears to be non-toxic, with mice showing none of the side effects typical of chemotherapy treatments, such as weight loss and neurological disorders. If these findings hold, it could pave the way for safe prophylactic drug regimens against cancer.
HAILING THE DRUG "TAXI CAB"
Taxol, a powerful chemotherapy drug, is deadly to tumors, cutting off their access to blood. But it has huge drawbacks. It usually lasts only a few minutes in the bloodstream as it's quickly broken down by the body's own defense mechanisms, so large doses are needed for it to work and even then its effect is weak. And worse, for the time it does last, it can cause serious damage to healthy tissue because of its toxicity. And because it's not water soluble, it can even slip past the blood-brain barrier, extending its toxic reach to the brain.
But Dr. Satchi-Fainaro and her team figured out a way to both get it past the immune system so smaller, more potent doses could be used, and eliminate its side effects. She and her team bound it to a polymer, "a carrier, like a taxi driver," she tells DOTmed Business News, "that will take it only to the tumor."
The polymer is an inert macromolecule -- it masks the drug so the immune system ignores it, and it's too large to leave the blood except in locations where the blood vessels are leaky. And these happen to be only at sites where tumor cells grow, and have recruited new vessels that feed them so they can swell in size, a process known as angiogenesis.
So now the polymer-bound drug can pass through the bloodstream unmolested, and then slip through the leaky blood vessels, where it can unleash its payload directly onto the tumor, choking its supply of blood and causing it to shrivel up to a harmless size.
BAD TO THE BONE
Dr. Satchi-Fainaro also looked to see if her technique could fight some of the most drug-resistant cancers known to medicine: cancers that have traveled from the breast or prostate and metastasized in the bone.
Dr. Satchi-Fainaro and her team first took some bisphosphonate, a family of drugs used to treat bone cancers and osteoporosis. She then tethered it to her conjugate of polymer and Taxol, attaching it with a molecule that is broken down by an enzyme in the body -- one highly over-expressed in bone tumors. So when the conjugate approaches a bone tumor, the bond is snapped and the drugs are delivered only to the cancer.
In mice, Dr. Satchi-Fainaro's drugs were able to inhibit about half of all growth of drug-resistant tumors. In other, more drug-sensitive, tumors, "[We] basically eradicated the tumor or tumor metastasis, or got them back to dormant size -- about one millimeter," she says.
"I'm very realistic," she says. "If I can regress the massive angiogenesis, and get [tumors] to regress to dormant size, it's basically transforming cancer into a chronically manageable disease, like diabetes. As long as we have drugs that are non-toxic, we can keep the tumors at this size and live like that [taking the drugs]."
Dr. Satchi-Fainaro thinks this "tumor dormancy model" will be most appropriate for populations like women with mutations to the BRCA1 or BRCA2 genes, who have such a high risk for deadly breast cancer they often have both their breasts removed in precautionary double mastectomies. "To those women," Dr. Satchi-Fainaro says, "this can be a much better physical prophylactic treatment."
Currently, Dr. Satchi-Fainaro is licensing this treatment to a pharmaceutical company (she won't say which), and is also trying to figure out why cancers seem to thrive in bones. "That's the six million dollar question," she says.