In Search of a Cure

By Linda Packer
In Search of a Cure

At IIT, dozens of students and faculty are pursuing cutting-edge research in cancer prevention and care. While they may be conducting their work quietly, they are being noticed. From a new $22 million grant to assess the relationship between cell phones and cancer to funding that supports innovations in x-ray imaging, IIT’s cancer researchers are leading a powerful search for a cure.

Jialing Xiang is standing at a table surrounded by bottles of chemicals and dozens of vials. In one corner of the Life Sciences lab a graduate student splits cancer cells and will store some of them in a huge vat of liquid nitrogen. Nearby, a Ph.D. student pours thick blue gel into a container in order to separate proteins.

They are looking for a suicide program gone awry.

In an engineering lab, Professors Miles Wernick, Yongyi Yang, and Jovan Brankov huddle around a computer monitor, viewing mammograms made with their new x-ray imaging technique. By producing highly detailed images of soft tissue, the method may take the guesswork out of breast cancer diagnosis, while also reducing the radiation dose to the patient. If approved by the FDA, it will represent the first fundamental change in the way medical x-ray images are made since their introduction in the late nineteenth century.

But there are engineering problems still to be solved.

IIT’s cancer research: a “little-known gem”

Although it might not be as well known as other on-going studies, cancer research is thriving at labs across campus. Teams from life sciences, engineering, and IIT Research Institute (IITRI) are facing the future head on, studying the drugs, treatments, and technology that may take us closer to finding a cure. And because they have no university hospital affiliation, they are conducting nearly every aspect of research directly on site.

“Cancer research at IIT is a little-known gem,” says F. R. McMorris, dean of the College of Science and Letters. “I don’t think most people realize that we have researchers delving into a number of significant issues, from understanding what prevents cancer cells from dying off naturally, to how to kill cancer cells without affecting healthy cells.”

Encouraging cell death by suicide

In life sciences, understanding the former is a work in progress for Jialing Xiang, assistant professor of biology. The adult body, she explains, has roughly 10,000 billion cells, and good health depends upon maintaining the right number. “There are two ways to do this,” she says. “One is to control the growth rate. The second is to control what we call a ‘suicide program’ or cell death program, in which the cells die by themselves.”

The cell death program is called apoptosis, which is Greek for ‘falling of leaves from a tree.’ As cells die by apoptosis, they literally fall off their supporting structure. The process eliminates extraneous cells, or cells that are already damaged.

The concept of apoptosis is just 30 years old, and Xiang is traveling down a little-chartered path. The conventional thinking is that cancer is caused by out-of-control growth; the newer concept is that it can also be caused by a dysfunction of the cell death, or suicide, program.

Xiang and her team are studying the program at the molecular level, trying to find out where and how apoptosis goes wrong. Why can’t certain bodies get rid of their bad cells? Why can’t they activate their suicide program? She is trying to find a clue that’s applicable for a variety of cancers- breast, prostate, leukemia, and neuroblastoma among them.

“The goal is to discover the problem and provide the information to drug designers for cancer prevention,” says Xiang. “Unless they know the source of the problem, they can’t find the solution.”

Stopping cancer from metastizing

Joy Chong, assistant professor of chemistry, is working on precision. She is developing cancer drugs that can be employed for a new cancer therapeutic technology called radioimmunotherapy (RIT). The goal is to provide a lethal dose of radiation only to tumor cells without causing radiation toxicity to healthy cells.

At the end of her research which, she cautions, is many years in the future lies the exciting possibility of cancer that can no longer metastasize, or spread from one part of the body to another.

“The effectiveness of the technology is based on two factors,” she says. One is the use of a “smart tracing agent” the result of an antibody binding with a toxin or antigen enzyme that is expressed on tumor cells. Using a synthetic linker, radiation is attached to the smart tracing agent, which attracts tumors. Then RIT employs tumor-targeting antibodies for highly selective delivery of the radiation, reaching the cancerous cells and minimizing the exposure of healthy, normal cells.

“This antibody-targeted radiotherapeutic approach is very promising,” says Chong, “in that a variety of tumor types can be selectively treated based on antigen-antibody affinity.” In addition to being effective on several types of tumors, the RIT drug has been shown to significantly enhance the overall response rate of treatment. Still another benefit: It is better tolerated in cancer patients than chemotherapy.

It is clear that the RIT technology cannot be effective without the appropriate drug. Chong is working to bring it to life and to eliminate the ability of the deadly disease to spread.

Halting cancer before it begins

At IITRI, researchers are working on preventing cancer altogether. Cancer research has been conducted at the institute since the 1960s, when IITRI was awarded a series of programs from the National Cancer Institute (NCI) to evaluate the activity of novel cancer drugs in experimental model systems. Within the following 30 years, IITRI researchers tested thousands of new drugs and natural product extracts, a number of which are now in common use in clinical oncology.

In the 1970s a separate initiative brought an NCI grant for researchers to study chemopreventive agents. “At the time chemoprevention was controversial; lots of people thought it couldn’t work,” says David McCormick, professor of Biology and senior vice-president and director of IITRI. “But we demonstrated very clearly in experimental model systems that it did work. IITRI was one of the first labs to generate significant data to show this was a viable approach for cancer control.”

In Search of a Cure
Rajendra Mehta is exploring the effectiveness of chemopreventives
Photo by Chris Kirzeder

Today, one chemoprevention researcher is Rajendra Mehta, professor of Biology, assistant vice president of IITRI, and head of IITRI’s carcinogenesis and chemopreventive division. His goal is to find a nontoxic chemopreventive agent that may also work on already-established tumors.

The method might be through dietary alterations. Or it might be accomplished by identifying a compound in what is known as a ‘functional food’ or a natural or synthetic substance, and providing that to high-risk groups.

Mehta is particularly interested in gauging the impact on breast cancer of a vitamin D analog, which may help patients who develop resistance to standard anti-estrogen treatment. He also is studying the impact of resveratrol, a substance found in grapes and red wine, on the prevention of lung cancer.

And he is working on formulating the chemopreventive agent not as a procedure, but as a pill, taken once a day.

Mehta’s project is one of approximately 20 active cancer research programs at IITRI. Last year the institute was awarded $28 million from the National Cancer Institute (NCI) for three five-year programs. The first is a $17.3 million program to study the toxicology of new drugs developed for cancer therapy. The other two programs total $10.8 million and support studies to identify new agents for cancer prevention and to study the toxicology and pharmacology of cancer preventive agents prior to their entry into clinical trials.

One of the studies concerns changes in gene expression in tumors in comparison to normal tissues. Over expression, McCormick explains, is “if a gene normally produces 50 of something, and this gene produces 100 or 200 or 500.” He continues, “If we can identify a gene that is over expressed in a particular type of tumor, it might be a good target for a cancer preventive drug. The argument goes that if we can prevent the over expression, we may be able to prevent the cancer.”

Two active programs are focused on identifying changes in gene expression that occur as a result of exposure to tobacco smoke and the influence of chemopreventive agents on those changes. IITRI molecular biologists are also collaborating with IITRI toxicologists to study the effects of chemopreventive agents on gene expression in normal tissues, with the goal of identifying early markers of toxicity.

Targeting specific organs

“IITRI chemoprevention programs include efforts to prevent cancer in a number of organ systems, with emphasis on the breast, prostate, lung, and colon,” says McCormick. These studies are designed both to evaluate the efficacy of new agents in experimental models for these cancers, and to support the development of the most active agents prior to their entry into clinical trials. Programs in cancer therapy involve studies of new vaccines and monoclonal antibodies, new drugs that are designed to target specific biochemical or molecular pathways essential for tumor growth, and traditional cancer chemotherapeutic drugs.

Still other studies include looking at pharmacokinetics, the study of patterns of drug absorption and clearance by the body. When the studies are completed, we may know how long drugs stay in the bloodstream, how they’re metabolized, and where they go after being administered.

IIT’s Medical Imaging Research Center

In Search of a Cure
MIRC’s faculty-researchers [left to right] Yongi Yang, Miles Wernick and Jovan Brankov are working to improve the detection of cancer
Photo by Chris Kirzeder

On the environmental side, IITRI recently received a $22 million grant from the National Institute of Environmental Health Sciences(National Toxicology Program) to participate in an international program studying the potential link between cell phones and cancer. The program will extend into 2011 and require the construction of a specialized laboratory facility. A group of scientists in Switzerland will build the facility and install it in IITRI’s labs, and a group of pathologists will be involved in an evaluation of the studies.

This is not the first time IITRI has been involved in such a project. A decade ago the institute participated in a study to see if 60 Hz magnetic fields, the type of fields generated by appliances and overhead power lines, were linked to cancer. The cell phone study will have broader participation and more money, and will generate the most detailed and thorough evaluation of cell phone frequencies that have yet been performed.

Groundbreaking cell phone study

In Search of a Cure
IITRI’s David McCormick, principal of the cell phone study
Photo by Chris Kirzeder

Last year at the Armour College of Engineering, IIT researchers established the Medical Imaging Research Center (MIRC), a group of faculty, staff, and students who are working in a collaborative environment to drive medical imaging as we know it into the next generation.

Many of MIRC’s research projects are targeted at the development of advanced techniques for cancer diagnosis and treatment planning. For example, Miles Wernick, associate professor of Electrical and Computer Engineering and Biomedical Engineering, along with his colleagues Jovan Brankov and Yongyi Yang, are continuing IIT’s tradition as a leader in the development of advanced x-ray imaging technologies.

“In standard x-ray imaging, the pictures aren’t very good,” says Wernick, who is also director of MIRC. “They do a particularly bad job of showing soft tissue. But conventional x-ray imaging is fast and inexpensive, so it is still widely used, especially in mammography.”

Whereas standard x-ray imaging measures only absorption of x-rays by the body, the new technology multiple- image radiography or MIR, can also measure two kinds of refraction effects, which are microscopic deflections of the x-rays as they pass through the body. This presents a much more detailed image than conventional x-rays.

“We have a $1.7 million grant from the National Cancer Institute to study the feasibility of using the MIR technique in hospitals for breast cancer imaging as a replacement for standard mammography,” says Wernick. And his team also shares a $3.5 million NIH grant with Rush Medical College to study the use of MIR imaging to assess cartilage degeneration in patients with osteoarthritis. If approved and adopted by the medical profession (“Getting people to change their habits can be difficult,” he says), this technology will represent the first fundamental change in how medical x-ray images are made since the discovery of x-rays in the 1890s.

Developing computer-aided diagnostic techniques

In addition to developing new imaging techniques, MIRC researchers are creating new tools to help radiologists make the best use of the images they have now. Yang, associate professor of Electrical and Computer Engineering, is taking the lead on a project to create a search engine that can access a large database of mammograms and recall those that are most similar to a given patient’s images. Since these historical images have known outcomes, they can be used as a frame of reference for diagnosing the patient’s condition.

One of the major elements of this and other computer-aided diagnosis techniques is a collection of algorithms that are used for automatically detecting and analyzing abnormalities in breast images. Yang and Wernick, working with Ana Lukic, a research associate in Biomedical Engineering, have developed advanced mathematical algorithms that find abnormalities in mammograms with much greater accuracy than existing techniques.

In other research sponsored by NCI, MIRC’s Mark Anastasio, assistant professor of Biomedical Engineering, is developing new imaging methods that will help physicians provide better radiation therapy to their cancer patients, while decreasing their radiation exposure. And Konstantinos Arfanakis, assistant professor of Biomedical Engineering, also of MIRC, is developing new MRI imaging methods that will help surgeons to avoid damaging vital nerves when removing brain tumors. “This is why the MIRC was created- to move medical imaging into important new directions,” says Wernick. “The work going on today in the MIRC won’t be in the clinic tomorrow, but several of our current projects could ultimately have a major impact on cancer diagnosis and treatment.”

Endings and beginnings: the research cycle

Although the outcomes of IIT and IITRI’s studies are as yet unknown, one thing is not: As these cancer studies move forward, other projects are gearing up. For example, IIT researchers will begin to look at the relationship between cancer and connexins. Connexins are components of ‘gap junctions,’ cell-to-cell channels that permit ions and small molecules to move between adjacent cells. They differ from tissue to tissue, and connexin mutations have been responsible for a number of different diseases, including deafness and peripheral neuropathy.

“In science, as one study is completed, another is underway. It’s a never-ending continuum,” says Dean McMorris. “When you solve one question, it raises questions about something else.”

And as Xiang says about whether cancer will be cured in our lifetime, “I hope so. It depends on how much we can dig out from this deadly disease.”

External Links:
National Cancer Institute

Can a glass of red wine or a cup of green tea really stop cancer in its tracks?

In Search of a Cure

Scientists are hopeful that chemoprevention, the use of natural or synthetic substances to prevent cancer before it develops, can reduce the chances of cancer in both high-risk individuals and in the general population. An effective chemopreventive agent may also reduce the incidence of second primary cancers in patients who have had their first cancer cured.

Although a new theory seems to surface every day in the popular press, a non-toxic chemopreventive agent that is 100 percent effective has yet to be developed. In an effort to achieve that goal, the National Cancer Institute is sponsoring a number of programs to identify and develop new chemopreventive agents. Cancer chemoprevention programs in progress at IITRI involve studies of a broad range of drugs and natural products, including

  • Lovastatin, a drug in wide clinical use for its activity in lowering plasma cholesterol
  • Analogs of vitamins A and D
  • Isoflavones and protease inhibitors derived from soybeans
  • Polyphenols isolated from green and black teas
  • Resveratrol, a potent antioxidant present in red grape skins