Cancer. The word can evoke fear in anyone, and its diagnosis can come like a thief in the night. The American Cancer Society reports that nearly 1 out of 3 people in the United States will develop some form of cancer in their lifetimes. While many strides have been made in the treatment and diagnosis of cancer, the 21st century promises to deliver a significant leap forward. And all signs point to engineering being at the center of those advances.
The good news is that the University of Illinois at Urbana-Champaign has a critical mass of researchers—both in natural sciences and engineering—committed to leading the way in finding next generation solutions to cancer and other medical challenges.
Last summer, the University opened the Cancer Center at Illinois, an interdisciplinary collaborative center directed by Rohit Bhargava, Founder Professor in Bioengineering. The Center brings together more than 90 faculty members plus undergraduate and graduate students, as well as postdoctoral researchers from across campus, to pursue cancer-related research.
In 2014, Bhargava introduced the Cancer Scholars program, which is enhancing the educational experience for a cohort of undergraduates in bioengineering through the lens of cancer. Supported by the College of Engineering, this program inspires students by integrating research with their education. Cancer is also a topic for an innovative program at the high school level, where the University brings together high school students from the Chicago area and Champaign-Urbana for an eight-week cancer-focused research and career development experience called researcHStart.
In the fall of 2018, the University will pioneer the first-of-its-kind, engineering-based Carle Illinois College of Medicine by receiving its first class of students, who will lead the next generation of innovation in cancer treatment and research.
“In the near future, we will need scientists and clinicians who will invent those tools and interventions that transform health care,” said Bhargava of the paradigm shift. “This is a new way to think about medical education and it’s really a new way to think about the future of medicine.”
Our extensive knowledge about cancer has primarily developed over the past couple generations. This is because prior to the last century, life expectancies didn’t allow for many forms of cancer to matriculate. Additionally, in recent years, the scientific community has gained access to more of the tools and technologies needed to understand cancer and its progression more clearly.
“Now is the time for cancer, Bhargava said. “It is rapidly emerging both in our population as well as in our scientific consciousness as a problem that engineering can tackle. Technology has reached a high level, even compared to a decade ago. The ability to measure images and store and analyze data is unprecedented, and technology is ubiquitous. Now we can think of different ways to tackle cancer, not only with traditional biology, but with new kinds of tools and technologies—with data and analytics and real-time monitoring devices to see if we can better understand cancer progression and control it.”
Although the Cancer Center of Illinois was announced during the summer of 2017, researchers have been collaborating on campus surrounding the topic for a number of years. Their goal is for the National Cancer Institute (NCI) to designate the University of Illinois as the first technology and engineering-focused cancer center in the nation. NCI has designated about 70 Cancer Centers to date, most of them (63) are involved in clinical care as well as research, some in public outreach. The other seven are engaged almost exclusively in research, with more focus on biology.
“Times have changed,” Bhargava said. “Although we have now discovered a lot, the question is how to take the basic knowledge and turn it into useful, impactful technology that benefits people. Can we create better drugs and better devices? That’s the job of engineers. We can provide a better way: higher quality cancer care, at lower cost, and for everyone.”
Although engineering has emerged as a new and critical piece of the solution of all of these challenges, the progress builds on decades of work done in other disciplines.
“Until now, cancer research has been largely descriptive,” Bhargava said. “There have been two major routes to describing it. One was its human and clinical impact. The second, a molecular understanding of cancer, which has made enormous strides in the past few decades. To really bridge those, we now need the tools from engineering and mathematics to describe that relationship and, of course, new technology to intervene.”
Imaging and Diagnostics
Traditionally, Bhargava contends, cancer has been diagnosed by its shape and size. Today, with the help of engineers, the goal is to diagnose more by its underlying molecular characteristics.
“The reason a molecular classification of cancer is so important is because drugs act on molecules,” Bhargava said. “If we can characterize cancer molecularly, we can better treat it. You can’t do that with current generation technologies. You really need next-generation technologies that are molecularly sensitive.”
Perhaps more encouraging is the possibility of a cancer diagnosis even before a solid tumor is formed. Researchers are using a process called multimodal multiphoton imaging to detect tumor cells which can tell a physician something about the molecular composition or functional metabolic changes of cells.
“What we have discovered is that the environment around a tumor changes because of the presence of that tumor,” said Stephen Boppart, another member of the Cancer Center of Illinois who is also Head of the Biophotonics Imaging Lab and Director of the Center for Optical Molecular Imaging. “It is an eye opener to realize that when a tumor begins, it sends out signals to the rest of the body to start changing its metabolism and its molecular composition. Those are early changes that we are trying to detect. It also tells us how aggressive that cancer will be and where that tumor might be growing.”
Boppart expects the technology to evolve over the next decade with these biomarkers, which get spread out very early in the disease, and carry the possibility of detection through routine blood or urine tests.
Currently, detection often comes from screening modalities (like X-ray mammography, or colonoscopy),” Boppart notes. “We use those modalities to look for masses or tumors that are millimeters in size, but a tumor of that size has been there for years. We need to shift toward molecular diagnostics to be able to detect early molecular changes.”
Brian Cunningham is a product of the University of Illinois’ Department of Electrical and Computer Engineering, having earned three degrees including a PhD from Illinois during the 1980s. His original research focus was on semiconductor crystal growth for laser detectors.
“At the time, there was no consideration to biology in any of those topics,” Cunningham recalled.
However, having lost both of his parents to cancer, he set out to think deeply about how he could use his engineering background to have an impact on human health.
He began working for Draper Laboratory where he helped develop tests to detect biomarkers for cardiac patients that would indicate whether or not they were likely to have another heart attack. He also founded a startup called SRU Biosystems where he helped develop sensors for identifying promising new drug candidates.
Today, Cunningham directs the Micro and Nanotechnology Laboratory at Illinois and is in his 14th year as member of the faculty with appointments both in bioengineering and electrical and computer engineering.
His numerous advances in imaging have included a photonic crystal biosensor microscopy, which can detect and image individual biological objects (e.g. cells, viruses, nanoparticles) for applications in viral load monitoring, ultrasensitive diagnostic tests for disease biomarkers, and imaging of live cell behavior.
Cunningham and his team are using the photonic crystal microscope as a platform for digitally counting molecules that are diagnostic for cancer. They have been developing ways to tag and count individual proteins or individual RNA molecules that they can detect out of a droplet of blood. These molecules indicate the presence of the tumor through proteins that are produced by the tumor or nucleic acids that are given off by dead cells that come from the tumor.
“When a cell attaches to a basement membrane, that’s the substrate upon which cancer cells proliferate or stem cells differentiate into other things,” explains Cunningham. “Now we can take images of this process over an extended period of time and see how those processes evolve.”
Robots and Imaging During Surgery
Boppart is developing a series of systems called “point-of-care technology,” one of which allows surgeons to use imaging capabilities to detect cancer cells in the operating room.
One out of three women who undergo a lumpectomy to remove a tumor in their breast need a reoperation because tumor cells are left behind. That’s because until this point, surgeons send the resected tissue to the pathology lab for pathologists to evaluate them under a microscope days later. Boppart and his team are developing a handheld imaging technology which will allow a surgeon to microscopically image the surface or margin of the breast mass, or even the tumor cavity, to determine if all the tumor cells are removed during the surgery.
“Using real-time optical coherence tomography (OCT), we can give a microscopic view to the surgeon, who can move the probe around the tissue and look for those cells, then intervene right then and there,” Boppart said.
Thenkurussi “Kesh” Kesavadas, the Director of Health Care Engineering Systems Center at Illinois, is working with Bhargava to develop a robotic device which uses molecular imaging to find the cancer cells so that those tissues can be removed during surgery.
“This merging of imaging and robotics is going to create new ways of removing cancer and reducing the cycle time from diagnosis to procedure,” Kesavadas said. “Through the combined technology, you can find cancer cells in the body and chase them to wherever they are. There are now small robots that can go search for tumors and kills cells. These technologies are going to become part of the treatment procedure in the next five or 10 years. It’s not science fiction anymore.”
Imaging and Treatment
Cunningham is also using photonic crystal microscopy in the context of looking at how cancer cells respond to drugs. Together with Brendan Harley, associate professor of chemical and biological engineering, he has been developing a model for glioblastoma (brain cancer) on the photonic crystal.
In collaboration with clinicians at Mayo Clinic, Professor Cunningham is also helping physicians to identify specific drugs for individual treatment of prostate cancer.
“In prostate cancer, there are many drugs the physician can choose,” explains Cunningham. “There is not any clinical guidance on which one will be the most successful for a particular patient. By identifying genes that are expressed by an individual patient’s tumor, you can have a clearer picture of what mechanism is the dominant one for that particular patient.”
Clinicians at Mayo Clinic take a droplet of blood from a patient, put it on a filter and send it to Cunningham. His team can extract the RNA from the strip of filter paper and test it with a sensor. They look for specific sequences of RNA that indicate specific tumor modalities in the prostate cancer. As they see these molecules go up or down, they can give feedback to the physician about whether the treatment is working or is starting to fail because the tumor has mutated in a new way and has become drug resistant.
“Our goal is to make cancer more of a chronic condition,” Cunningham explained. “As the tumor itself changes, physicians can adapt treatment based on genomic data rather than a best guess.”
Understanding and controlling the growth of blood vessels, the supply lines of the human body, can also play a role in drug development. Princess Imoukhuede, an assistant professor of bioengineering, and her team have uncovered signally activity that directs that blood vessel growth and influences the progression of cancer.
“If we learn how the proteins fit together and cause protein function, then you can imagine that drugs can be developed that block the way things fit together and other drugs can be developed that enhance how things fit together,” Imoukhuede said. “Unlocking this understanding would lead to better drug design for treating several diseases including cancers and even cardiovascular diseases.”
“No longer will there be silos between different disciplines in medicine, but truly an integrated approach to detecting and treating disease,” Boppart said.
Among the objectives of the Cancer Center of Illinois is creating engineering systems that give researchers the tools they need to make sense of the exploding amount of data and devices created to augment human performance.
Computing becomes increasingly important when studying cancer from the molecular level. This is especially important in drug development. Consider that, according to Bhargava, only about five percent of drug trials actually make it through to become a new drug. By better understanding and predicting each trial through more accurate data evaluation, we could drastically increase the speed and proficiency of development. The University of Illinois is in a position to leverage its expertise and across multiple displines to create new compounds that can be used to develop those drugs.
“The second part is to look at model systems,” Bhargava said. “We don’t think cell lines that are grown in a Petri dish, for example, are faithfully reproducing cancer behavior. We engineers want to use things like 3D printing to design new materials and replicate cancers and test them in the lab.”
“In the coming years, you are going to see the merger between personalized genomic medicine and personalized detection,” Boppart added. “We have such a wealth of technology. The greater challenge is how to make sense of all this information. That’s where the computing, machine learning, deep learning and artificial intelligence are going to come into play.”
Technology has enabled our everyday items to become more personalized, and that is certainly the direction medicine is heading as well. Boppart, for instance, has created a “Doctor’s Office of the Future” in one of his labs at the Beckman Institute. When it comes to diagnosis, doctors will have more personalized data at their fingertips.
“We built this space as one example of how we think technology will be integrated in that doctor-patient experience,” Boppart said. “If we want to improve our detection of disease, we really think we need to advance the technology at the front line.”
These advances will provide doctors with more tools for disease prevention and early cancer detection, as well as helping to anticipate the possibility of recurrence.
Patients will also play an important role, which will mean fewer visits to the doctor’s office. For instance, wearable devices created at Illinois are capable of monitoring physiological vitals like blood pressure all the time. Furthermore, Cunningham is developing a series of technologies called “lab on a smartphone” which would allow a patient to conduct medical detection tests using their mobile phone's built-in camera and high-resolution spectrometer.
“An MRI is expensive, but taking a droplet of blood from the finger is pretty non-invasive and enables a physician to have a clearer idea of what is going on,” Cunningham adds.
Because genetics play such a key role in cancer, Cunningham predicts that in the future, more and more people will have their genomes sequenced as a matter of choice.
“If you have a tumor, it’s likely the tumor is going to be sequenced to determine not only which genes have been mutated, but also what those mutations actually mean in terms of biochemical pathways that take place in the tumor itself,” Cunningham said.
"If we can image early enough, perhaps we can treat early enough,” Bhargava notes. “If we can understand all the key factors that drive cancer, then we can intervene in multiple ways, designing a system of therapy as opposed to a single-drug. Finally, we will give survivors the technologies to make sure cancers don’t recur or if they do, to be able to treat them immediately. If you think about all three—early detection, multi-system therapy, and monitoring—these are really engineering problems. Once you understand that process, I think it’s obvious why engineering matters for cancer in the future."
“Today we appreciate even more how advances in technology can lead to new discoveries in biology or new diagnostics for medicine,” Boppart concluded. “We are going to continue to see this grow. With the Cancer Center at Illinois and our engineering-based College of Medicine, there is an incredible momentum that we have been building here. We’re really at the forefront of leading these changes.”
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