Shrinking the war on cancer

Michael Cima's wife referred to the meetings as his ''Wednesday poker nights," but, to the chemical engineer, they were more like cram sessions for a college exam. Cima had never done cancer research before, but every Wednesday for months he met with some of the top scientists in the field including a Nobel Prize winner.

Cima may have been hazy on the details of cancer biology, but he had an idea that impressed the high-powered group from MIT and Harvard Medical School: creating a microchip that could detect various types of cancer far earlier than current tests. The chip would use incredibly tiny objects called nanoparticles to look for the earliest signs of cancer -- from inside the patient.

''I would really like to see the simplest of these devices starting to be used in cancer research studies in three years," said Cima, a professor at Massachusetts Institute of Technology. ''The idea of being able to do this [in a person] is where we're heading."

Non-cancer scientists such as Cima are helping to create a whole new approach to the diagnosis and treatment of cancer, one that confronts the nation's number two killer at its most fundamental level.

Nanoparticles -- so small that 80,000 could fit across a human hair -- may be able to slip unnoticed inside cancer cells to deliver medicines, or latch onto cancer cells so that doctors can see tumors more easily. The trick will be learning how to control these tiny particles, which behave in different and unexpected ways from larger objects.

''Nanotechnology will have a transformative effect on cancer diagnosis and treatment," Dr. Andrew von Eschenbach, director of the National Cancer Institute, predicted earlier this month, in announcing the latest grants in a $144.3 million federal push to bring nanotechnology into cancer research. ''Its impact is already visible."

But just barely.

Though nanotechnology has been around for more than 20 years and nanoparticles can be found in consumer products from tennis rackets to stain-resistant shirts, nanotech is still relatively new to the medical world. So far, only a handful of cancer medications, such as a new formulation of the breast cancer treatment taxol, employ nanoparticles.

The new Center of Cancer Nanotechnology Excellence at MIT and Harvard, which received a five-year, $20 million grant from Eschenbach's agency this month, is expected to play a lead role in spreading the nanotech gospel, in part by recruiting non-cancer specialists like Cima and Angela Belcher, a young chemist who last year won a $500,000 MacArthur Foundation ''genius grant" because of the promise of her work in nanotechnology. In addition, Center for Cancer Research director Tyler Jacks recruited two of MIT's most eminent biomedical researchers, 1993 Nobel Prize winner Philip Sharp and biotech pioneer Robert Langer, to play lead roles.

''The best way MIT can deploy its assets in the war on cancer is to bring together people like Bob Langer and Phil Sharp on the same problem," said Jacks.

The researchers face significant hurdles in adapting technologies from electronics and materials science to cancer treatment, where the safety standards are much higher. For instance, Belcher hopes to use tiny crystals called ''quantum dots" that literally light up when they find cancer particles. But today's quantum dots originally developed for the solar power industry, are made of cadmium and are toxic to humans, so she will have to find new, safer materials.

Scientists say now is a good time for cancer research to get small. The completion of the Human Genome Project in 2003 created an inventory of the 20,000 to 25,000 genes needed to make a human being and triggered a boom in the new field of proteomics, aimed at understanding the proteins that genes produce. Two years later, researchers have identified roughly 100 cancer ''biomarkers" -- the proteins and other chemicals that tumors generate.

Nanotechnology could give researchers the tools they need to put all this new information to use.

''It's one of those paradigm shifting technologies," said Dr. Anna Barker, deputy director of the National Cancer Institute, which has been funding nanotechnology projects for seven years. ''Science at the nano level is extremely important in understanding [cancer biology]. We've needed nanotech to interrogate cells at that level."

In the MIT-Harvard group, Dr. Ralph Weissleder of Massachusetts General Hospital will direct one of the most clinically advanced projects, developing nanoparticles that reveal whether cancer has spread -- or metastasized -- beyond the initial tumor site.

Conventionally, oncologists must remove a patient's lymph nodes to see whether cancer has spread, but Weissleder's magnetic nanoparticles are designed to bond with cancer cells and show up on an MRI scan. Already, his team has injected the particles into hundreds of prostate cancer patients and found metastatic cancers so small they likely would have been missed by surgeons.

The cancer-sensing microchip project is also beyond the blackboard phase. Cima and Langer have developed chips to hold nanoparticles that would either detect cancer biomarkers or track concentrations of chemotherapy drugs. The device must be extensively tested in lab animals, however, before it could be implanted in the first human.

Langer, an authority on drug delivery with over 500 patents for his innovations, first suggested 11 years ago that nanoparticles containing drugs could be targeted directly at prostate cancer cells, a potentially huge advance over the more shotgun approach of conventional chemotherapy.

''One of the problems with cancer therapy is that it goes everywhere in the body," Langer said, often killing healthy cells in the process.

Now, Langer and his former student, Dr. Omid Farokhzad of Harvard Medical School, will attempt to make his vision a reality. They hope to attach medicines to tiny bits of RNA, which, like ''homing devices," would head to the cancer cells and drop off their tumor-killing cargo. The idea is elegant, but Langer acknowledges there are high hurdles to cross such as isolating the RNA particles he wants to use and then finding a safe way to deliver them to the patient.

Langer has been down long roads before. Thirty years ago, he and Dr. Judah Folkman identified the first technique for cutting off the blood supply to a tumor, a field that produced its first approved treatment -- the drug Avastin -- last year. ''I know how hard it is to go from a concept to actually helping people," Langer said. But, looking at the nanotechnology projects his group is taking on, he concluded, ''I don't view any of them as impossible."

Scott Allen can be reached at allen@globe.com.