Tiny new weapon for war on cancer
Houston scientists have devised an ultrasmall “smart drug” that eludes all biological barriers and withholds the release of its poison until it is inside the heart of cancer cells that have spread to the lungs, one of the primary causes of cancer deaths.
In a mouse study published this week, the nanotechnology-based strategy destroyed a particularly lethal type of breast cancer after it reached the lung, a stage of the disease considered almost untreatable. The team hopes to test the strategy on patients next year, and other scientists said the findings should stimulate research with additional drugs and cancer types.
“If this bears out in the
clinic, even in a small fraction of what we’ve seen in lab experiments, it will be transformational, the firstever demonstration of a cure of metastatic disease to the lungs,” said Mauro Ferrari, president and CEO of the Houston Methodist Research Institute and the study’s principal investigator.
The study, published in the new edition of Nature Biotechnology, found that 50 percent of mice treated with the therapy had no trace of the disease in their lungs after eight months, the equivalent of about 24 years of survival in humans. The disease currently kills patients six months to two years after it spreads to the lungs.
Cancer researchers were quick to note that curing cancer in mice is a long way from curing the disease in humans. Sheathed in silicon
Any effective treatment of metastatic cancer would represent a huge advance in therapy, which today is often effective when tumors are detected while still local but is usually ineffective when they’ve spread to other organs. The five-year survival rate for breast cancer, for instance, ranges from 100 percent to 72 percent in the early to intermediate stages, then falls to 22 percent after it’s metastasized.
One big problem is that only a small portion of a given dose of cancer drugs reaches the target. Drugs have to contend with the body’s defense mechanisms, which attack intruders. They also must get past cancer’s own barriers, which include proteins that act as tiny pumps to drive the drugs outside malignant cells and prevent them from accumulating within. The result is that healthy tissue absorbs much of the drugs, resulting in side effects and continued cancer growth.
The Houston team’s research relies on nanotechnology, the engineering of functional systems at the molecular scale, some 100,000times smaller than the width of a hair. The field hasn’t delivered the breakthrough drug many had predicted, but Ferrari said the new strategy may “provide answers to why the transformation hasn’t been profound and why its time may now be here.”
The strategy works in steps, ferrying a standard chemotherapy near the nucleus of the metastatic cancer, then tricking the tumor into swallowing the drug’s poison.
“It’s a great piece of work, novel and unique, the sum of the parts greater than any individual aspect,” said Dr. Steven Libutti, director of the Montefiore Einstein Center for Cancer Care in New York. “As a baby boomer, I find it reminiscent of the moon mission, the way the drug-delivery system’s components separately complete their tasks.”
Ali Khademhosseini, a Harvard nano researcher, also praised the research’s “clever way of generating nanoparticles up taken by cells directly in the tumor.” He said the method is “highly innovative and could result in improved therapies downthe road.”
Ferrari’s team developed porous silicon particles as drug carriers, able to travel unimpeded through healthy blood vessels thanks to their small size and disc-like shape. At the tumor site, the silicon breaks down, generating the cancer-killing nanoparticles. The nanoparticles, coiled into tiny balls that resemble cancer cells, are absorbed and taken to the cancer nucleus, where the drug is released.
The particles encase doxorubicin, a potent chemotherapy that, used conventionally, prevents tumor cells from dividing but causes adverse effects in the heart. No approach in humans has been able to deliver it only to the tumor, a limitation to the drug’s effectiveness and safety.
The strategy benefitted not just the 50 percent of mice who were diseasefree eight months later, but also the half that didn’t respond as well. They lived an average of 160 days, the human equivalent of three to six years longer than metastatic breast cancer patients on standard chemotherapy. The study involved triple-negative breast cancer, a hard-totreat variety that doesn’t respond to strategies that effectively target the more common types. Works for several types
Dr. Haifa Shen, the study’s co-senior author, said the results promise particularly life-saving potential because the approach worked even though the mice were genetically engineered to be resistant to chemotherapy.
The approach also worked in a small portion of mice in which the breast cancer spread to the liver, the other most common destination of cancer spread. A related strategy, using some of the same steps, has shown promise in the third most common site of such metastasis, bone marrow. The technique does not appear to work in brain cancer metastasis, the fourth most common destination.
Ferrari said he’s hopeful the approach revives the potential of existing drugs.
“People keep looking for new drugs to kill cancer, but I think a lot of the fights can be won delivering the drugs we have in more complete fashions,” Ferrari said.