Science is more than theory and lecture. Science is fun. Science is hands-on. Science is…
Barrie Bode never set out to be a cancer researcher. He just kind of “wandered into it.”
In graduate school, Bode conducted research aimed at expanding knowledge of the biochemistry and metabolism of a normal human liver. He was particularly interested in how the liver regulated the transport and metabolism of an amino acid known as glutamine.
A year after earning his Ph.D., he came across two lines of cells from a cancerous liver. On a whim, he measured the rate of glutamine import into those cancer cells—and was stunned to find it was about 10 times higher than normal. That observation changed the course of his life’s work. It also led to the identification of two specific amino acid transporters that are elevated in a wide spectrum of primary human cancers and aid tumor growth.
For the past two decades, Bode has been working to develop highly targeted therapies to slow the uptake of glutamine and other nutrients that feed cancer. His research group today includes three NIU Ph.D. students, one student working on a master’s degree and four undergraduates.
“After I made that initial finding, I knew I wanted to work in research on cancer because it’s such a scourge of a disease,” says Bode, chair of NIU’s Department of Biological Sciences.
Bode will give a public talk on “Combatting Cancer in the 21st Century” during a STEM Café event from 6:30 to 8:30 p.m. Tuesday, March 24, at Eduardo’s Restaurant, 214 E. Lincoln Highway. In advance of the presentation, the NIU Newsroom caught up with Bode for a Q and A on the topic of cancer research. What follows is a condensed version of his responses.
Where do we stand generally in the fight against cancer?
These are exciting times. The scientific knowledge emerging annually is staggering. And it’s really revealing the complexity of these diseases that we collectively call cancer. We are light years ahead of where we were just 20 years ago and are learning new things about the biology of cancer literally each week.
In fact, we’re generating so much data now—including sequences of nucleic acids, sequences of expressed proteins within a tumor, the chemical signatures of metabolic systems—that there is a little bit of a bottleneck. It’s not a dearth of data that’s limiting medical researchers but the necessary analyses of the available and emerging data. Those analyses will ultimately reveal cancer’s complex fabric and vulnerabilities.
Do you think there will be a cure for cancer in our lifetimes?
No. It’s still going to be a long road, but there is good news for cancer patients.
Cancer is just a catchall phrase for dozens of different diseases that have the same endpoint—uncontrolled growth of tissue driven by mutated cells. Each cancer is complex and different, and even within a tissue there are distinct forms or cancer—different kinds of colon, breast, liver and brain cancers, for example, all driven by unique mutations and behaviors.
Some types of cancer might be cured—that’s happened already. But new pharmaceutical cures are rare. Over the next century, I’d say the chance is very remote that we will find a single ‘cure for cancer.’ Instead, treatments will become more refined and targeted, informed by the science and technologies that are available so that cancer can be managed much like other diseases, such as heart disease and diabetes. The plasticity, or ability to change, of cancer cells will require that these treatments be modified over time.
The good news is that the explosion of knowledge, better detection methods and new or improved therapies are resulting in improved longevity and quality of life for cancer patients. Doctors are already finding more precise ways to target cancerous tumors for treatment while sparing healthy tissues, meaning fewer side effects. Down the road, I think we’ll be able to further extend lifespans and improve quality of life through these management strategies.
It seems like cancer touches all of our lives in some way. Why is it so prevalent?
First, we’re better at detecting it. Second, cancer is a disease of aging, and as healthcare in general improves, people are living longer. With each passing year of life, our chances of getting cancer increase.
Also, from an evolutionary standpoint, there are no selective pressures against cancer as it relates to aging. It could be a naturally selected process—part of a mechanism for generational turnover. That would mean we’re fighting against our own biology and its inherent complexity.
How does cancer kill?
Tumors can be deadly in a number of ways. Metastatic cancer—or cancer that has escaped, migrated and spread beyond the primary tumor—is typically the deadly form. As metastases become pervasive in the body, they can cause organ failure or muscle wasting. Cancerous tumors consume nutrients and starve healthy tissues. That can cause a number of secondary effects. A lot of cancer patients will die of infection because the immune system is weakened, either by the cancer or by treatments for the cancer. Others die of dehydration secondary to organ dysfunction in late-stage disease.
What are some of the most common forms of cancer treatment, and why don’t they always work?
Surgery, chemotherapy and radiation are the three most common types of cancer therapy.
Both chemotherapy and radiation aim to stop cancerous cells from replicating through various mechanisms, such as by breaking a cell’s DNA or inhibiting its ability to manufacture the building blocks for DNA synthesis. On the downside, standard therapies sometimes make people very sick because they’re indiscriminate in the effects on the body and attack normal dividing cells such as hair follicles, gut epithelial cells and white blood cells – leading to hair loss, nausea and immunosuppression, respectively. So chemotherapy or radiation may cause tumors to shrink but they also can have negative effects on healthy tissues or systems.
Some cancers are difficult to eradicate because they are very good at two things: hiding and adapting. For instance, when patients undergo a round of chemotherapy, often the tumors will shrink. The problem is the residual disease. Through several different mechanisms, the residual disease can become resistant to the therapy. So it can lie dormant and then reemerge—more often than not with the same properties that made it resistant to the first-round of therapy.
What are some of the most promising areas of research, in your opinion?
I think my research group is working in one of the hot areas of cancer research—identifying unique metabolic changes in cancer and developing ways to slow, stop or exploit these changes. We’re not alone in this pursuit. There is also a new generation of drugs targeting molecular processes that seem to be unique to cancer cells. One example of a success story would be Imatinib, or Gleevec, a small molecular inhibitor that obstructs a specific protein that stimulates the spread of cancer cells in patients with chronic myeloid leukemia (CML). It has been highly effective in patients with a specific mutation that drives CML.
Cancer biology research is also leading to individualized treatments. Doctors sequence a patient’s DNA and/or exome—the cohort of expressed genes in a tumor—and look for molecular signatures or mutations to develop highly targeted therapies for that person. This is happening right now. In fact, in some cases at large medical centers, patient tumors are being grafted and grown in mice. Then clinicians test panels of different drugs on the mice and look for regression to assess the best form of treatment, informed by the genetics of the patient’s own tumor.
But with every new step, comes troubles. This sequencing is incredibly expensive, as are many of the drugs. Also, some patients don’t have time to wait months for studies on mice to be completed. I know of one researcher who is working to overcome the delay by using fly models, instead of mice.
Then there’s the FDA approval process. Individual patients can consent to the use of experimental drugs, but the clinical trials needed to bring new drugs to the fore generally take years.
What are some of the hottest areas for students interested in becoming cancer researchers?
While we need good people in all facets of cancer research, bioinformatics, or the blending of computer science and biology, is the fastest growing field in biology right now. Graduates trained in bioinformatics are needed to generate discoveries by parsing and analyzing biological data. They are a hot hire at drug companies and research universities, and they command very good salaries.[NIU offers an undergraduate course in bioinformatics and a master’s degree in biology with a specialization in bioinformatics.]
What is the state of funding like for cancer research?
There is a lot of cancer research going on, but there could be much more. The National Cancer Institute receives about 11 percent of the National Institutes of Health budget. The NIH budget likewise is about 10 percent of the national defense budget. So by deduction, we’re funding cancer research at a penny for every dollar of defense. This level of funding is insufficient to support discovery of new therapies for a group of diseases that impacts everyone’s life directly or indirectly. Research grants are highly competitive. In fact, I have some colleagues bailing out of the field because they can’t get funding to continue their research programs.