April 4, 2012 | 6
Chemotherapy treatment for cancer is a nasty process. Doctors must try to give patients just enough of the toxic drugs to kill off cancer cells without doing too much harm to the rest of the body’s healthy tissues, a balancing act that, even if successful, can nevertheless cause horrible side effects.
But what if you could program the harsh medicine to go only to the cancerous cells, sparing the rest of the body? Researchers have been aiming for this goal for more than 100 years and have achieved some success in targeted treatment by using monoclonal antibodies in immunotherapy. Getting chemotherapy to cancer cells, however, has proved difficult. A new nanotechnology might just finally bring it into reach.
Scientists have spent the past few decades tinkering with nanopaticles, and recently they have been able to cover them with cancer-seeking proteins and load them with a tumor-busting drug. But these tiny particles, hundreds of which could fit across the width of a human hair, have so far failed to perform in humans.
A new tumor-targeting, nanoparticle-based compound called BIND-014 is now in clinical trials in people, after showing promise in both mice and monkeys. Although this first trial is small, with only 17 patients, and still ongoing, researchers are reporting some positive results, and no obvious major safety setbacks, according to a paper published online April 4 in Science Translational Medicine.
The researchers could move quickly from animals to human studies because they relied on components that have already been used in humans. Specifically, they loaded the nanoparticles with the chemo drug docetaxel, which used to treat solid tumors in many parts of the body, including breast, head, lung, neck, prostate and stomach. They then outfitted the particles with a well-known tumor-specific antigen that targets newly forming blood vessels that develop to feed tumors and that’s also present in prostate cancer cells.
But the researchers did not just slap a few proteins on a nanoparticle and send it into tests. They screened more than 100 different nanoparticles with various sizes, surfaces and drug-release capabilities. “Previous attempts to develop targeted nanoparticles have not successfully translated into human clinical studies because of the inherent difficulties of designing and scaling up a particle capable of targeting, long-circulating via immune-response evasion and controlled drug release,” study co-author Robert Langer of the Massachusetts Institute of Technology said in a prepared statement.
In the current, phase 1 safety trial, patients with advanced or metastatic cancer received an injection of the nano-drug once every three weeks. The drug seemed to remain in the body for at least two days, giving it time to do its damage on the tumor cells. And damage it has seemed to do. Although final results from the trial will be forthcoming, tumor growth has slowed in many patients, and in some, tumors have been shrinking—or even going away. In one 51-year-old man with bile-duct cancer, the researchers found that several metastases had shrunk to near vanishing after just two doses of relatively low concentrations of the nano-drug. And the tonsil tumor of a 63-year-old patient shrank by about 25 percent after two doses as well. The researchers were all the more surprised at these early findings because in traditional forms, docetaxel has not proved to be terribly effective against many types of tumors in the study.
“The emerging BIND-014 clinical data showing signals of efficacy even at relatively low doses validates the potential for the revolutionary impact of nanomedicines and is a paradigm shift for the treatment of cancer,” Philip Kantoff, of the Dana-Farber Cancer Institute and co-author of the new study, said in a prepared statement.
Because the particle homes in on cancer cells specifically, the drug is delivered to the tumor site in much higher—and thus more effective—concentrations than it is via standard plasma-based injections. The particles themselves also seem to have a good size and shape to evade the immune system, and they also shows low accumulation in the liver, suggesting they are relatively safe.
Still, considering the larger debate about the safety of nanoparticles, this nanomedicine will require further testing in this and future, larger trials. But, as the researchers noted in their paper, this compound has shown progress toward the century-old goal of creating a cancer treatment that “can increase efficacy and decrease toxicity.” In other words, they hope we are finally nearing a time when we will be able to kill off the cancer—and the treatment’s side effects.
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