The crucial and potentially fatal problem with breast cancer has remained a mystery for more than a century: Why do different kinds of breast cancer cells tend to spread to specific organs, such as the brain, bone, or lungs? That’s the killer. Now the National Science Foundation has given Shelly Peyton of the Chemical Engineering Department at the University of Massachusetts Amherst a mandate to address this key problem in a totally new way by awarding her a $590,000 grant for 36 months.
Peyton actually engineers authentic replicas of brain, bone, lung, and other tissues in her lab and will use them to develop very patient-specific drugs to block breast cancer from spreading. Her lab is the only one in the world employing this promising new method.
“What we’re trying to understand is why breast cancer doesn’t spread randomly,” explains Peyton. “It almost always ends up in a few areas of your body, and that’s what makes it so deadly. Ninety percent of breast cancer deaths are due to metastasis. So the ability of breast cancer to spread to your brain, your lungs, your bone, your liver, and take over those organs, that’s the real danger.”
Peyton’s engineering approach to breast cancer could unlock a century-old riddle. More than 100 years ago, Dr. Stephen Paget reported a measurable inclination for secondary breast cancer metastases to occur in specific organs. This non-random metastasis is commonly referred to as “tissue tropism,” and intensive study by thousands of scientists has never explained it.
“The reason why it has been so hard to figure out is that I think we’ve been studying it the wrong way,” says Peyton. “Cancer biologists typically come from a chemical/genetics background. So they say, for example, we know this kind of cell tends to go to bone, so let’s look at its genetic code and see how it differs from cells that tend to go to lungs.”
But the baffling thing about breast cancer is that it’s so heterogeneous. There are wildly different breast cancer cells from patient to patient and case to case.
“So it’s just so difficult to make connections that way,” notes Peyton.
Instead, Peyton will face this challenge by coupling her engineering expertise in biomaterials development, systematic measurement of biological processes and response, and statistical modeling.
Basically, what Peyton is doing in her lab is manufacturing disease models ex vivo, or outside the body. By using biomaterials to build brain, bone, lung, or other tissues, she can then introduce various kinds of breast cancer cells to test how they interact. With this kind of highly controlled experimentation, the lab can then record all the results in a complex data set and feed it into a computer model, similar to the kind used in population statistics.
She expects this model to evaluate exactly why specific kinds of breast cancer cells migrate to specific kinds of tissues.
“I think there must be some sort of physical determining factor, given how different these various tissues are,” says Peyton. “Brain is sort of soft gray matter tissue, bone being very dense and hard, lung being full of blood in an oxygen-rich environment. Our approach is trying to replicate those target tissues in the lab to look at their physical interaction with diverse breast cancer cells.”
Peyton’s plan is to correlate all these results so her lab can identify or create a drug for each specific cell-tissue interaction and each specific patient.
“So we not only want to kill the breast cancer cells, but block their ability to spread to certain potentially fatal tissues elsewhere in the body,” says Peyton. “That would be a really powerful combination therapy geared for each individual patient.”
The grant is co-funded by the NSF Biomaterials Program, the NSF Biotechnology, Biochemical, and Biomass Engineering Program, the NSF Materials and Surface Engineering Program, and the NSF BioMaPs Initiative.
As part of this grant, Dr. Peyton is collaborating with the College of Engineering Diversity Program Office to form an educational outreach program targeting high school teachers and female students titled “Engineering the Cell: A Bioengineering Experience for Young Women.” This program will integrate research and education by training both students and high school teachers in a laboratory setting, and allowing teachers to take laboratory modules back with them to the classroom. (August 2012)