Cancer genetics/precision medicine cluster hire to bring new focus on pharmacogenomics to School of Pharmacy

By Katie Gerhards

In 1965, a diagnosis of acute lymphoblastic leukemia (ALL), the most common childhood cancer, was essentially a death sentence: only 4 percent survived.

Researchers at St. Jude Children’s Hospital led the exploration of genetic technologies to see what made the fortunate 4 percent different, in order to better predict who would respond well to traditional treatments, and who in the remaining 96 percent should be treated more aggressively.

St. Jude researchers have spent decades working to personalize ALL treatment, and their work has more than paid off. Today, the five-year survival rate (which often means the patient is cured), is 85 percent.

“With the recent initiatives at UW–Madison, this campus can and should be a driving force pushing these technologies forward to improve patient outcomes.” –Arash Bashirullah

This type of radical transformation in cancer treatment is what’s possible with precision medicine and pharmacogenomics, says Arash Bashirullah, associate professor in the Pharmaceutical Sciences Division of the University of Wisconsin–Madison School of Pharmacy.

“With precision medicine, you can essentially fingerprint a tumor, find characteristics that would make it more susceptible to certain drugs, and thereby identify which drugs will be most effective for each patient,” says Bashirullah. “With the recent initiatives at UW–Madison, this campus can and should be a driving force pushing these technologies forward to improve patient outcomes.”

Bashirullah was instrumental in getting the School of Pharmacy involved in a cluster hire initiative that aims to enhance UW–Madison’s research into personalizing cancer treatment. The campus-wide cluster hire initiative entails three new faculty positions across the UW–Madison School of Medicine and Public Health, School of Pharmacy, and Law School. The upcoming hires will focus on different aspects of precision medicine:

• Delving into the genetics of human cancers at the School of Medicine and Public Health
• Investigating how individuals respond to targeted drug therapies at the School of Pharmacy
• Understanding the legal and ethical issues involved with genetic testing at the Law School

Critical role of pharmacogenomics

Precision medicine is essentially personalized therapeutic intervention, which can be tailored to the individual as well as their unique disease. The new position within the School of Medicine and Public Health, likely to be housed in the Department of Oncology or McArdle Laboratory for Cancer Research, will be focused on the manifestation of cancer itself—tumors.

“One goal of oncology is to be able to identify the tumor type and catalog all of the genetic markers to determine which drugs are most effective with which genetic profiles,” says Bashirullah. “The more that catalog is built up, the more you can sequence patients’ tumors and recommend appropriate therapies.”

“While this area of investigation is relevant to geneticists, bioinformatics, pathology, and medical oncology, the unique position of experts in pharmacy and pharmaceutical science is the focus and expertise on drug mechanisms.” –Mark Burkard

An example of this type of decision-making in action is with triple-negative breast cancer. With that diagnosis, the cancer isn’t supported by estrogen, progesterone, or HER2 receptors, which means that it won’t respond to therapies that target those hormones or receptors. Patients with triple-negative breast cancer require a different type of therapeutic intervention than those who don’t.

On the other side of the same coin, the new position within the School of Pharmacy, which could land in either the Pharmacy Practice Division or the Pharmaceutical Sciences Division depending on expertise, will focus on pharmacogenomics—the patient’s response to drug therapies.

“Certain drugs will be very toxic to some patients and not to others,” he says. For example, some people might metabolize drugs faster than others, which could mean that drug is neutralized and will have no impact, or it could generate a toxic metabolite.

“These differences exist within a normal population,” says Bashirullah. “The idea is to identify these variations in the patient’s genome and combine these insights with the genetic susceptibilities of the tumor, in order to select the most effective and least toxic treatment.”

Pharmacogenomics aims to identify genetic markers to help with medication management. One of the “hot” areas of this investigation right now is in using biomarkers to predict benefits of immunotherapy, according to Mark Burkard, associate professor in the Department of Medicine. Existing biomarkers—such as microsatellite instability and tumor mutational burden for immunotherapy—offer only limited ability to predict which individuals will benefit.

Although progress is being made, establishing more drug-biomarker pairs is critical to advancing medicine.

“While this area of investigation is relevant to geneticists, bioinformatics, pathology, and medical oncology, the unique position of experts in pharmacy and pharmaceutical science is the focus and expertise on drug mechanisms,” says Burkard, who is serving on the search committee for the School of Pharmacy’s new pharmacogenomics faculty position.

“This is especially relevant now with the explosion of clinical genomics information based on the development and implementation of high-throughput DNA sequencing technologies,” Burkard adds.

Growing precision medicine on campus

Several of the School’s faculty members, including Bashirullah, already have a focus on genetics. But by adding a new dedicated pharmacogenomics researcher to its ranks, the School of Pharmacy is among those leading a widespread shift toward growing precision medicine expertise at UW–Madison.

“Adding pharmacogenomics expertise to the School will be important both for research and for education of our students,” says Paul Marker, associate dean for research and professor in the Pharmaceutical Sciences Division. “We’re moving toward a future where patients’ drug therapy will be tailored to them as an individual, and to push that vision forward, the School of Pharmacy needs high-quality research in that area.”

Barry Gidal, professor and chair of the Pharmacy Practice Division, says adding a pharmacogenomics faculty member will enhance our students’ understanding of how genetics affect dosing, as well as how to interpret genetic information for clinical applications.

“Pharmacogenomics is still a relatively new field, and with this new faculty member, the School will have the opportunity to influence where this field of research goes,” says Bashirullah.

The School of Medicine and Public Health recently launched the UW Center for Human Genomics and Precision Medicine, which will include a research component as well as diagnostic facilities.

“We’re moving toward a future where patients’ drug therapy will be tailored to them as an individual, and to push that vision forward, the School of Pharmacy needs high-quality research in that area.” 
–Paul Marker

“Having the Center for Human Genomics and Precision Medicine on campus means that there are incredible built-in resources for collaboration, growth, and synergy,” Bashirullah explains.

Burkard hopes that, in addition to the new center, the School of Pharmacy’s new pharmacogenomics faculty member will work in tandem with the UW Carbone Cancer Center’s precision medicine researchers to accelerate the incorporation of next-generation sequencing (NGS) into clinical settings, which can uncover disease susceptibilities as well as inform treatments.

By building a focus on pharmacogenomics, the School of Pharmacy will help to advance the field of precision medicine and bolster the UW–Madison health sciences campus’ continuous efforts to improve patient care.

The search for the School’s new pharmacogenomics-focused faculty member is already underway, with plans to have the hire begin in early 2019.

Read about another initiative at the School of Pharmacy to improve the efficacy of drug therapies: the Wisconsin Center for Nanobiosystems (WisCNano).

Learn more about UW–Madison’s cluster hire initiatives.