MIT is at the forefront of the next major leap in the fight against cancer, which claims eight million lives per year. In this new era, life scientists and engineers are joining forces — and working directly with clinicians — to transform cancer from a death sentence to a manageable disease.
“This represents MIT’s best opportunity to contribute to the cancer problem. Our unique strength is this remarkable mix of scientists and engineers, who are committed to coming together to work in a new space — a space defined by the intersection of their disciplines,” says Tyler Jacks, director of the David H. Koch Institute for Integrative Cancer Research.
The Koch Institute’s predecessor, the Center for Cancer Research established in 1974, was also a radical enterprise. It aimed to “know the enemy” by discovering the genetic origins and molecular processes of tumors. This approach yielded fundamental advances, such as the identification of the first human cancer gene, which led to lifesaving new treatments.
Now, MIT’s life scientists are tapping into the problem-solving expertise of engineers. “They think about pathways in cancer differently from biologists. Their backgrounds prepare them to think about complexity and network behavior, and allow them to do mathematical and computational modeling that’s more sophisticated than what typically trained biologists do,” says Jacks.
The Koch Institute also interacts with oncologists, hospitals, and biotechnology companies to expedite innovations to the clinic. Several collaborations are under way, including the Bridge Project, a historic partnership between MIT and the Dana-Farber/Harvard Cancer Center.
Jacks says, “Whether it’s new drugs, new devices, or new approaches, we’re intent on translating our discoveries into more immediate benefits to patients.”
Silencing cancer genes with nanotechnology
Sangeeta Bhatia’s laboratory recently engineered a nanoparticle that, in a mouse with human tumors, successfully delivered a therapy called siRNA to silence a gene found in ovarian cancer.
“It worked better than anything we’d tried before. It shrunk the tumors and prolonged survival. We were thrilled,” says Bhatia, the John J. and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science.
RNA interference, or RNAi, is one of the most promising new cancer treatments on the horizon, because of its potential to silence many cancer genes at once. But deploying disruptive snippets of genetic material, known as siRNA (short interfering RNA), in tumor cells has proven difficult.
Bhatia’s experiment to clear that hurdle benefited from the expertise of her collaborator, William Hahn, who knew which gene to target.
Hahn, a professor of medicine at Harvard, an oncologist at the Dana-Farber Cancer Institute, and a genomics expert at the Broad Institute of MIT and Harvard, leads a team that is systematically screening ovarian cancer cell lines looking for genes essential for these cells’ survival. He likens his part in the collaboration to “coming up with a parts list. You need to have a parts list of what’s broken before you can think in engineering terms of how you fix this problem.”
With Bhatia’s nanoparticles, researchers could rapidly and efficiently sort through this “parts list” — consisting of perhaps 200 or more genes — silencing certain ones to understand their function within a tumor’s molecular machinery.
That, in turn, enables much faster discovery of which genetic culprits to target with treatment. Bhatia says, “Our collaboration has really accelerated the science.”
Decoding drug resistance
Alice Shaw and Forest White are working to understand how some non-small cell lung tumors, which are the deadliest of all human cancers, quickly evade new treatments that target genes implicated in that type of cancer.
“If we had a better understanding at the molecular level of what has gone wrong in these resistant cells, that might lead us to other therapies or combinations of therapies which work better,” says Shaw, an oncologist and molecular geneticist at Massachusetts General Hospital. Through its clinical investigator program, the Koch Institute invites physician-scientists like Shaw to conduct, and bring a caregiver’s perspective to cancer research at MIT.
Shaw and White have recently teamed up to study resistance to targeted therapies. Using samples selected by Shaw from drug-resistant patients, White, a bioengineering professor, feeds them into a mass spectrometer to measure protein molecules. The device analyzes the hundreds of protein modifications that make up the complex signaling network between tumor cells.
“Tumor cells are constantly adapting to their environment. We’re actually able to see which pathways are being turned on in response to the [cancer drug],” says White. “It is valuable to work with somebody who actually sees patients and can tell us the most important questions to ask, and where our technology will be applied best.”
Within the first few months of their collaboration, Shaw and White have already seen encouraging results. They hope to soon verify a resistance mechanism in one type of non-small cell lung cancer that could be targeted by new or existing drugs. White says, “If you take away enough of the survival mechanisms, then you can kill the tumor.”
“Check engine” light for cancer
What if doctors could track tumors in real time as they respond to chemotherapy or show signs of metastasizing? It would be a potentially lifesaving leap over the current method of diagnosis: a surgical biopsy of cancerous tissue that offers only a snapshot of the disease.
“Two months down the road, that information may not be relevant. What if I could leave something behind during that same procedure that I can interrogate via MRI weeks later?” says Michael Cima, the Sumitomo Electric Industries Professor of Engineering. An accomplished inventor, he has 45 patents and has co-founded several companies.
Cima and his collaborator, electrical engineering and computer science Ph.D. student Christophoros Vassiliou, developed what Cima calls a “check engine” light for tumors: a tiny device filled with nanoparticles that signal cancer’s presence and can be detected by a noninvasive MRI (magnetic resonance imaging) scan. Importantly, the monitor can be implanted via a biopsy needle. “I could put this in front of physicians, and they wouldn’t even need to read the instruction manual,” says Cima.
An earlier prototype accurately detected and monitored cancer in mice. For his graduate thesis, Vassiliou improved on that design in two ways: tailoring the implant to fit inside the bore of a biopsy needle, and incorporating an amplifying component to boost the nanoparticles’ weak magnetic signals. “This is an electrical engineering problem,” he says. “The research is characteristic of what the Koch Institute wants to push forward — having people from different backgrounds working together.”
Plans are under way for testing the device on cancer-stricken dogs, whose tumors are more similar to those of humans, and Cima believes the implant will be ready for human trials within five years.
Cancer tricks the immune system into overlooking malignant cells. Experimental DNA vaccines have successfully programmed immune cells to recognize and target cancer cells, but so far they have failed to elicit a sustained defense.
Paula Hammond and Darrell Irvine are developing a new drug-delivery technology that could bring an effective cancer vaccine a step closer. Administered easily and painlessly through the skin, it could deliver not only the DNA that programs the immune response, but multiple other agents to boost that response.
“In terms of vaccines, this is still new territory. But it might not be far around the corner, because it’s showing a lot of promise,” says Hammond, the Bayer Professor of Chemical Engineering. She is an expert in assembling ultra-thin films composed of sequential layers of organic compounds. The layers can be tuned to disperse or dissolve in stages. Irvine is a professor of materials science and engineering and biological engineering who specializes in novel approaches to immunotherapy.
Their technology involves applying a multilayered film to a surface patterned with microneedles. The needles do not reach the skin’s pain receptors, but they do penetrate the epidermis, which is dense with “first responder” immune cells that trigger their relatives within the body to destroy a pathogen.
In an experiment on a mouse, the microneedle array deposited its coating, which in turn delivered two layers: one containing DNA, which provoked an immune response, and another containing a type of nanoparticle used in drug delivery.
“The coated microneedles have the potential to act as multifunctional delivery platforms, carrying cargos with diverse physical properties,” says Irvine. The ultimate goal is to add layers that contain vaccine boosters and other drugs designed to stimulate the immune system.
Hammond says that her fruitful collaboration with Irvine came about because the “Koch Institute provides the opportunity for investigators to talk to each other and work together. That is definitely a change for us. We’re able to actually talk about how cancer functions, and that gives us ideas about how we can address it. That has been incredibly meaningful.”