Solving the Breast Cancer Puzzle
- Tuesday, Oct 15, 2013
In recognition of National Breast Cancer Awareness Month, read about biomedical engineering faculty members who are making strides in cancer research.
The way Stanislav Emelianov puts it, Mother Nature presented us with the puzzle of breast cancer. But Mother Nature has also provided the tools with which we solve the puzzle.
Emelianov and other researchers in the Department of Biomedical Engineering at The University of Texas at Austin give Mother Nature a boost with their engineering acumen and innovation.
They are finding ways to detect breast cancer more effectively, diagnose the types of cancer more precisely, treat it more directly and enhance the quality of life for survivors.
In Emelianov’s case, he and his team are engineering nanoparticles that can extract information from cancer cells and relay the information to physicians in real time.
Faculty members in the Cockrell School of Engineering are also working with tools and materials that enable them to attack cancer at the molecular and cellular levels, where the most effective research can be done.
And there’s still a lot of work to do.
The American Cancer Society estimates that in 2013 in the United States there will be more than 232,000 new cases of breast cancer and more than 39,000 deaths from breast cancer.
In recognition of National Breast Cancer Awareness Month, here are a few snapshots of how Cockrell School’s biomedical engineering faculty members are using their engineering expertise and sophisticated means to make differences in cancer research.
Cracking the Matrix
Laura Suggs, associate professor
A woman is able to find a tumor in her breast because the tumor’s stiffness stands out from the rest of the breast tissue.
Besides alerting the woman to a possible problem, there’s other information that can be obtained by studying the degree of the tumor’s rigidity. For example, research shows that the stiffness drives metastasis, which is the spread of the cancer to other parts of the body.
Laura Suggs and her research assistants laboratory are working on a way to determine the role of tumor stiffness in metastasis. It could help to develop methods of detection and treatment.
She and her lab have engineered a material that can be stiffened or softened with infrared light. The material, a hydrogel that carries nanoparticles, mimics the extracellular matrix around a cancer cell. The extracellular matrix is just outside the cell and is made up of proteins and other materials.
“We use our light-emitting system to dial stiffness up or down, and then we look at rates of metastasis,” Suggs said.
That enables researchers to see how the extracellular matrix reacts under different circumstances such as the presence or absence of drugs. They also could simulate different stages of cancer.
The goal is to help drug developers and physicians determine effective therapies and when to use them. Suggs is working with a $900,000 grant from the Cancer Prevention and Research Institute of Texas.
“What we want to know is: can we inform drug therapies or clinical trials of drug therapies based on what we know about matrix stiffness?” she said. “Is there some optimum stage at which we should give drugs? Should we not give drugs while the tumor’s soft and give drugs while the tumor’s stiff?”
Suggs’s interest in engineering hydrogels is at the heart of the research.
“The engineering is being able to control matrix stiffness with the light source,” she said. “That’s really novel. Imagine if you could take a light and shine it on concrete and make it harder or softer. That’s what we’re doing, except that we’re doing it with a hydrogel.”
Keeping Cancer Out of Circulation
Aaron Baker, assistant professor
Aaron Baker and his researchers study the cardiovascular and lymphatic systems that carry blood, oxygen and nutrients throughout the body.
Those systems also carry cancer, which becomes much harder to treat once it jumps on those circulatory highways and spreads to other parts of the body. About 90 percent of cancer deaths occur after a cancer has metastasized.
But, Baker said, there’s little work being done on how to prevent cancer from getting access and moving along those systems.
Baker and his lab are working on what could be a big step toward setting up a circulatory roadblock. They want to make it possible for drug developers to test drug compounds to determine whether they have the potential to prevent cancer from spreading.
The device they are developing simulates the flow of the cardiovascular and lymphatic systems and could be used with the automated systems that drug developers employ to test the potential effectiveness of drugs.
“It creates flow in this standard culture format that allows robotic pipetting and other drug screening facilities to assay for whether cancer cells stick with their drug,” Baker said.
The device could help drug companies open another way to fight cancer.
Baker and his lab have made a prototype device using a $25,000 seed grant from the Texas 4000 student organization. Texas 4000’s signature event is an annual bicycle rides of more than 4,000 miles from Austin to Anchorage, Alaska, to raise money for cancer research, treatment and survivorship.
Baker’s lab works with breast cancer cell lines provided by UT Southwestern in Dallas.
“When we look at cancer cells adhering to lymphatic endothelial cells that line these lymphatic vessels what we’re doing is looking at one of the primary ways breast cancer spreads,” he said.
Baker has applied for a patent for the device and is seeking more funding to develop it further.
A More Diplomatic Cancer Solution
Jeanne Stachowiak, assistant professor
Cancer cells, by their very definition, are abnormal. They proliferate faster, consume more resources and go places they’re not supposed to.
A less studied way to keep cells from going down the path of abnormality is to manipulate how they communicate with each other via channels called gap junctions. It’s an area that’s getting attention from the laboratory of Jeanne Stachowiak.
Gap junctions are protein channels that extend across a cell’s membrane border and connect with gap junctions of other cells. When a cell starts to act up, its neighbors send messages through the gap junctions to rein it in.
Cancer cells, determined to take over the cellular neighborhood, aren’t interested in hearing those messages and thus stop producing gap junctions.
Stachowiak and graduate student Avinash Gadok are using donor cells to make materials that can be injected to restore gap junctions to cancer cells.
“We’re making membranes that are heavily enriched with these junction proteins and delivering them to tumor cells to see if we can reconnect the cells and reestablish their communication pathways with neighboring healthy cells,” Stachowiak said.
Instead of going to war with cancer cells by killing them and quite possibly damaging healthy tissues along the way, the gap junction method is more of a diplomatic solution.
“A better approach than killing tumor cells, if it were possible, would be to just convince them to behave normally,” Stachowiak said. “This idea of normalizing cells has been attractive for a long time but there just haven’t been super effective ways of doing it.”
So far, it seems possible. They’ve had success in experiments with tissue cultures. Now, they want to try normalizing cells with 3-D tissue cultures and in animals. They’re exploring collaborations with Carla Van Den Berg and Hugh Smyth, professors in UT Austin’s College of Pharmacy, to further the research.
Stachowiak started the project with a $25,000 seed grant from Texas 4000, a student group that raises money to fight cancer with an annual bike ride of more than 4,000 miles to Alaska.
Besides delivering messages to the misbehaving cells, the injected gap junction proteins could carry drugs and chemotherapeutics, Stachowiak said. The delivery would be targeted to specific cells, bypassing their membrane barriers, potentially delivering drugs more efficiently than current drug and chemotherapy treatments can.
Making Sure to Get It All
James Tunnell, associate professor
A surgeon strives to remove all cancer cells from a woman’s breast when a lumpectomy is performed.
Sometimes, however, follow-up tests reveal that the knife didn’t get all the cancer along the border between the tumor and the healthy cells. And another surgery has to be done.
James Tunnell and colleagues are developing imaging technology that would enable surgeons to identify all the cancer cells during the procedure.
The technology builds on the use of nanoparticles to identify cancer cells. Nanoparticles are microscopic units that are used in a variety of applications in science, medicine and even consumer products, depending on their composition.
Fluorescent nanoparticles seek out and cling to cancer cells. This helps diagnosticians and surgeons hone in on exactly where cancer cells are in the body.
“The particles essentially label the cancer cells,” Tunnell said.
Tunnell, who works with imaging technologies, and his team developed a device that can capture images of the particles during surgery.
A problem with this type of imaging during surgery is that the fluorescent particles are obscured by blood and tissue.
“What this system gets around is being able to correct for those distortions that happen while you’re doing the imaging,” Tunnell said.
He said it could be compared to radar that lets pilots see through clouds or fog to view what’s on the ground.
While the technology was developed for treating breast cancer, Tunnell said it could be used for other types of cancer in other parts of the body.
He’s worked with Dr. Sunil Krishnan, radiation oncologist at MD Anderson Cancer Center, Brian Korgel, a professor in the Cockrell School’s Department of Chemical Engineering, and Jon Schwartz of Houston-based Nanospectra Biosciences.
Reducing Collateral Damage
Amy Brock, assistant professor
Amy Brock is investigating ways to treat breast cancer that reduce the harmful side effects of many therapies.
One strategy Brock and her lab are researching is a way to “rehabilitate” cancer cells.
“Rather than attempting to kill every cancerous cell, we would like to ‘reprogram’ them so that they behave just like normal, non-pathological breast cells,” she said.
Brock also is investigating using the breast’s milk ducts as a channel to deliver drugs to treat breast cancer. With direct delivery into the breast through intra-nipple injection, drugs would not have to pass through other parts of the body.
The lab uses computational models to gain insight into the wiring diagram genetic networks of tumor cells and conducts a variety of wet lab experiments to test the predictions, she said.
Brock brought her research interests, which include investigating male breast cancer, with her from her graduate and post-doc experiences.
Before coming to UT Austin nine months ago, she had been a fellow at the interdisciplinary Wyss Institute for Biologically Inspired Engineering at Harvard University. There she focused on preventing mammary tumor progression in a transgenic mouse model.
“We developed a method for localized RNA silencing in the ducts of the mouse mammary gland that dramatically reduced tumor incidence from 100 percent to 25 percent,” she said.
Brock, who is working with startup funding, said that while researchers continually gain knowledge about the breast, there is much that remains a mystery.
“But this is an exciting time because new tools in systems biology have made it possible to track various interacting and dynamic factors simultaneously,” she said. “As we gain a better understanding of the underlying biology of breast cancer, we'll be able to develop ways to prevent the disease in the first place.”
Working to Make Reconstruction Better
Mia K. Markey, associate professor
Women who have their breasts surgically removed because of cancer or the threat of cancer still have a big decision to make: should they undergo breast reconstruction.
That decision and the range of issues it entails is full of uncertainties. What will the reconstructed breasts look like? How will they feel? How long will the process take? What will the psychological impact be?
Mia K. Markey is leading a wide-ranging project that will help women make better decisions about reconstruction.
Questions of body image and appearance are of great concern to women considering reconstruction. That’s why, Markey said, the project places great emphasis on psychological as well as physiological issues.
“Our interest is in trying to quantify appearance changes and to relate that to measures of psychological functioning,” she said.
In 2012, 91,655 women had breast reconstruction procedures, according to the American Society of Plastic Surgeons. That was down 5 percent from 2011, but 16 percent higher compared to 2000.
In the project, researchers are gathering information that includes photos and measurements of women before and after mastectomies and during the reconstruction process as well as biomechanical measurements to see how women move.
They also collect psychological information about women undergoing reconstruction — what the women expect before starting, as they go through it and after it’s completed.
A look at the major collaborators provides an idea of the mix of disciplines and institutions involved in the project.
They include Krishnaswamy Ravi-Chandar, professor in the Department of Aerospace Engineering and Engineering Mechanics at UT Austin; Fatima Merchant, assistant professor, Department of Engineering Technology at the University of Houston; and Michelle C. Fingeret, associate professor, Department of Behavioral Science, Dr. Gregory P. Reece, professor, Department of Plastic Surgery, and Dr. Scott B. Cantor, Department of Health Services Research, all at The University of Texas MD Anderson Cancer Center in Houston.
The team works with 3dMD, an imaging company based in Atlanta.
The project is funded through grants from the National Institutes of Health and the American Cancer Society.
The project’s goal is to develop a system that would provide women with accurate information. It is based on what each woman says she wants in her reconstruction and the body of scientifically collected information provided by hundreds of women who have shared their experiences in the project.
Markey added that the system also could help predict costs and the time it would take to complete the reconstruction.
“One of our long-term goals is to see whether we can help people choose a reconstruction process up front and get them more quickly to an outcome that maximizes psychosocial adjustment,” she said.
All-In-One Cancer Tool
Stanislav Emelianov, professor
When the technology that Stanislav Emelianov and his laboratory are developing reaches its full extent, it would offer physicians a Swiss Army knife for treatment of breast cancer.
Instead of blades, can openers and toothpicks, the tool Emelianov is developing would deploy sound, light and nanotechnology to detect, treat and monitor the disease. The specificity with which the tool will perform will offer a large degree of personalized medicine.
Emelianov is working with a grant from the Breast Cancer Research Foundation to research and develop the technology.
The system starts with basic ultrasound, a technology so safe it’s used to image and monitor babies in the womb. It adds light in the form of a laser to an ultrasound system to produce photoacoustic images of tissue.
“We will be able to see tissue anatomy and structure, blood flow, … and also how much oxygen there is in the primary tumor and lymph nodes,” said Geoff Luke, a member of Emelianov’s lab who is working on the technology. “Based on those things alone we think we can dramatically improve diagnosis in real time, right there in the clinic.”
To the light and sound, Emelianov adds nanoparticles. And these aren’t just any nanoparticles.
“They are sensors, not just simple agents,” Emelianov said.
In effect, the nanoparticles interact with the cancer cells to gather information, such as what kind they are and if there’s more than one type of cancer. Then, by changing optical properties, the nanoparticles deliver new information to the physician via the ultrasound/photoacoustic imaging system.
Other types of nanoparticles, loaded with drugs, could be delivered to the cancer cells in a highly targeted way. Another treatment would be to heat nanoparticles that have matched up with cancer cells to obliterate the cancer cells while keeping the healthy tissue nearby unharmed.
Luke will take his newly conferred Ph.D. degree and the technology to MD Anderson Cancer Center in Houston with the aim to use it in a clinical setting with people.
The technology won’t be ready overnight, Emelianov said, but he is optimistic about its prospects. More importantly, he said, physicians he’s talked to about it are optimistic, too.
It offers a ray of light — and sound — in the treatment of breast cancer.
Written by Tim Green