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IU cancer scientist: Seeking to uncover the genetic blueprints that might foretell treatment woes

While a boy, Bryan Schneider lost his grandmother to cancer. Although young at the time of his grandmother's death, he still remembers that his relationship with her was a close bond. Her cancer diagnosis and subsequent death left an impression on him that would steer him toward a career in medicine.

The Jasper, Ind., native and associate professor of medicine and medical and molecular genetics also possesses a life-long interest in chemistry. "I've been a science geek since I was a little kid. I definitely ruined multiple carpeted areas in my parents' house with chemicals," he said with a smile while seated in his Indianapolis office.

"I loved the idea of being a doctor or surgeon," said Dr. Schneider, also a physician/scientist at the Indiana University Melvin and Bren Simon Cancer Center and the Shawn Hanson Investigator in Breast Cancer Research.

Bryan Schneider

Bryan Schneider

Print-Quality Photo

By the time high school rolled around, Schneider definitely knew he wanted to be a physician, and he set his goal on getting into medical school. He selected IU School of Medicine among his offers. By his third year in medical school at IU, he said he "felt a real comfort in taking care of cancer patients. I could sense that they felt comfortable with me because I wasn't afraid to ask them questions that were difficult because of my personal experience with cancer."

During a fast-track residency -- two years instead of three -- Schneider found himself learning from the likes of George Sledge Sr., an internationally recognized breast cancer expert. "To say I was blown away by his interaction and style with his patients is an understatement," Schneider said. On the research side, he was learning from David Flockhart, an international authority on how individuals respond differently to medications. Both men would become mentors.

While a fellow, Schneider began a real-world study -- a study to examine whether the genes of women without breast cancer were different from those with the disease. He and several colleagues developed the procedures and protocols for collecting, processing, and storing specimens from women without breast cancer. They designed a questionnaire, recruited volunteers, and managed the data. They went to work during the 2005 Komen Indianapolis Race for the Cure. Thus, a project called Friends for Life was born.

The result? They collected more than 1,200 blood samples the day of the race. Equally important, the event proved that women would willingly donate blood or tissue to help the fight against breast cancer. Schneider's Friends for Life played a crucial role in the establishment of the Susan G. Komen for the Cure Tissue Bank at IU Simon Cancer Center two years later. The bank, led by Drs. Anna Maria Storniolo and Susan Clare, is the world's only repository of blood and tissue samples from women without breast cancer. Because of the tissue bank, researchers from around the world are now studying the differences between healthy and cancerous tissue.

In addition to understanding the genes that cause cancer, Schneider is passionate about understanding how the genetic variation that makes each of us different might also impact how we respond to a drug. Following in the footsteps of his mentors, he seeks to understand how our genetic blueprint affects the efficacy of a drug and the side-effects to individuals caused by that drug.

"It is clear that in the clinic different patients experience different benefits and different degrees of side-effects despite using the same drug at the same dose. I believe that, on some level, this is likely dictated by our genetic blueprint," he said.

Based on some of his early work in this area, he earned a $5.8 million Promise Grant from Susan G. Komen for the Cure in 2009. With the Promise Grant, Schneider and colleagues hoped to establish biomarkers that physicians can use to better predict which breast cancer patients will benefit from specific treatments and which cancer patients will suffer significant side effects.

Schneider and colleagues have done just that as they recently identified a genetic biomarker that causes neuropathy among some breast cancer patients using a class of chemotherapy drugs called taxanes. Neuropathy is a nerve problem that can cause pain, numbness, tingling, burning, or muscle weakness in different parts of the body, especially the fingertips and feet. Most concerning to Schneider "is that this side effect can really adversely impact daily functioning for some patients. In fact, for some it is a life-long problem even long after they are cured," he said.

It is one of the first genetic biomarkers to have been reported for neuropathy caused by taxanes, which includes paclitaxel or Taxol. The finding may eventually lead to a blood test to determine if a patient is at risk of developing neuropathy.

"We found multiple, provocative genes that may be associated with neuropathy, one of which stood out from the rest in a gene named RWDD3," Schneider explained. They found the gene by conducting a comprehensive genetic look at more than one million genetic variations in each of the 2,204 breast cancer patients studied. The patients were enrolled in the Eastern Cooperative Oncology Group clinical trial E5103.

The IU investigators looked for variations in DNA called single nucleotide polymorphisms or SNPs. They identified genetic subgroups that were likely to develop neuropathy. Those who carried two normal nucleotides in the RWDD3 gene had a 27 percent chance of experiencing neuropathy. But those who carried one normal nucleotide and one SNP had a 40 percent chance, and those who carried two SNPs had a 60 percent chance.

The study also found that older patients and African Americans were much more likely to have neuropathy.

Schneider will advance this research with additional trials to validate these findings and to determine whether a different type of taxane therapy would result in less neuropathy in the more susceptible genetic group.

Schneider's research caught the attention of the world's leading oncology organization, the American Society of Clinical Oncology (ASCO). ASCO asked Schneider, also an associate director of the Indiana Institute for Personalized Medicine, to present his research during its annual meeting in Chicago this past spring.

Additionally, last month the Conquer Cancer Foundation recognized him as the recipient of the 2011 Advanced Clinical Research Award in Breast Cancer. The $450,000 award will further Schneider's research on taxane-induced neuropathy.

For Schneider -- who has yet to turn 40 -- he need only look to his office bulletin board filled with notes, postcards and photos from patients and patient families for inspiration to continue his work, both in the lab and clinic. "The collection on my bulletin board is more than mementos," he said. "It's a constant reminder that cancer is more than a disease. I keep them because it serves as motivation to me."