The University of Minnesota is one of two sites in the world for Bank on a Cure, an innovative endeavor to collect DNA from patients with multiple myeloma to advance research on the cancer and enhance treatment for patients.

Just as we look different on the outside, our bodies are different on the inside, too. Our risk for disease, response to drugs, and millions of other attributes are encoded in our DNA.

"That's why, even though we think of multiple myeloma as a single disease, it really isn't," says Brian Van Ness, Ph.D., professor and head of the University of Minnesota's Department of Genetics, Cell Biology and Development. Van Ness conducts research on multiple myeloma through the University's Cancer Center.

"We have a clinical definition of the disease, but everyone responds differently to treatment, based on individual genetic make-up," he says.

Such thinking reflects how biomedical research has changed its focus since the mapping of the human genome in 2002. And, in few areas is this change greater than in cancer research. Now, research and treatment focus on understanding the biology of how cancer cells work at the molecular and genetic levels and how individual patients or sub-groups of patients respond to drugs. Consequently, oncologists can make treatment more individualized and targeted than in the days when they had little to offer their patients but massive doses of toxic drugs to kill their cancer. The massive doses often caused tremendous collateral damage to the body.

Still, questions remain. Why do some patients respond well to a particular drug? Why do others experience nothing but negative side effects with little impact on their cancer?

"The goal is to predict drug efficacy and toxicity based on a patient's genetic profile, and ultimately develop individualized assessments and predictions for the right drug at the right dose for the right patient."
— Brian Van Ness, Ph.D.

These are questions that Van Ness is tackling in his research. He is a member of the Cancer Center's research group on the genetic mechanisms of cancer and specializes in multiple myeloma. His laboratory is developing cell lines and mouse models to explore how different genes can influence the progression of myeloma and the response to treatments. He also works with national and international groups conducting studies to correlate genetic variations with disease outcome and patients' responses to different drug therapies.

Van Ness notes that new drugs need to go through an extensive testing and approval process before they can be prescribed. But despite this intensive process, drugs react differently in different patients.

Patients vary in the ways they absorb, distribute, metabolize, and transport drugs across cell membranes. For example, patients who are resistant to a type of drug may have cells that transport the drug out of the cell before it has had a chance to work.

"Individual variations in genes that regulate these biologic processes may not only impact efficacy, but can significantly influence adverse effects," says Van Ness. "The goal is to predict drug efficacy and toxicity based on a patient's genetic profile, and ultimately develop individualized assessments and predictions for the right drug at the right dose for the right patient." That will offer the dual benefits of avoiding unnecessary treatment for patients less likely to respond to a particular drug, and targeting treatments more closely to those patients who will benefit.

Bank on a Cure

One of the great challenges with genetic research is that investigators need an enormous pool of patient information to validate research findings. With more common types of cancer, such as breast cancer, it's easy to get sufficient numbers of patients' DNA. But with myeloma, a less common cancer of the bone marrow, researchers must cast their nets globally to gather a sufficient pool of DNA samples from patients.

To do that, the International Myeloma Foundation (IMF) in 2003 launched Bank on a Cure, the first global, myeloma-specific DNA bank. Van Ness, who is a senior IMF scientist, was named co-director. He had previously established the molecular genetics lab for the Eastern Cooperative Oncology Group, the largest phase III cancer clinical trials group in the country. (Phase III trials compare the results of people taking a new treatment with the results of people taking the standard treatment.)

Van Ness' expertise made it logical for the IMF to locate one of its two physical DNA banks at the University of Minnesota. The other is in London, England. This groundbreaking effort involves the majority of major myeloma centers worldwide and thousands of myeloma patients who donate DNA samples to the Bank. The project fosters collaborative research, providing researchers with access to complete genetic information with a goal of collecting up to 10,000 samples from myeloma patients.

Developing the technology to manage these DNA samples was a major accomplishment. Bank on a Cure's scientific team researched over one-half million genetic variations that can affect cancer and targeted 3,400 genetic variants that may influence cell growth and therapeutic responses. They designed the prototype for a myeloma-specific gene-testing chip. The technology identifies genetic variations in the DNA, which provide the basis for studies identifying factors relating to disease onset, symptoms, clinical response and drug toxicity.

Myeloma and Beyond

The knowledge gained from Van Ness' research and the DNA chip technology applies to diseases other than multiple myeloma, including other cancers, neurological disease, cardiovascular disease, and lupus. Such strides in the field of molecular genetics have become a catalyst for a crossdisciplinary focus on the emerging field of pharmacogenomics at the University of Minnesota.

Pharmacogenomics is the science of understanding the correlation between an individual patient's genetic make-up and his or her response to drug treatment. This collaboration combines the expertise of University researchers in medicine, biostatistics, pharmacy, genetics, and molecular biology, to name a few, as well as collaboration between the University and Mayo Clinic.

Ultimately, according to Van Ness, this collaboration will allow speedier and more cost-effective drug development, with better results for patients. He predicts: "Drug treatment based on genotype will become the standard of care in coming years for patients with cancer and other diseases." And the University of Minnesota and its Cancer Center will have played a key role in making the standard reality.

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This story was originally published in the University of Minnesota Cancer Center 2007 Annual Report.