January 21, 2021

New Carbone Cancer Center researcher turns to tumor DNA in bloodstream to improve cancer diagnostics

Madison, Wis. — Even during medical school, Muhammed Murtaza, MBBS, PhD, was already thinking about the possibilities of lab science, and what he might be able to accomplish.

Like discovering new, more effective ways of finding and diagnosing cancer.

“I was clearly more interested in the challenging questions we face on a daily basis in medical practice, compared to the delivery of care itself,” Murtaza said. “You can translate a number of questions from the practice of medicine back to the bench and try to answer those questions.”

That strong desire to advance research, along with a deep interest in molecular biology, genomics and big data, led him to pursue a PhD in medical science, with a specific interest in non-invasive cancer genomics. He later founded his own research group at the Translational Genomics Research Institute (TGen) in Phoenix, Arizona.

Now, he’s bringing all that experience, and much more, to the UW Carbone Cancer Center. Hired as an associate professor in the division of surgical oncology in October 2020, his goal is to work across disciplines to push precision medicine and molecular cancer research forward.

“Cancer is really a disease of the genome, driven by mutations that happen across the DNA,” Murtaza said. “So we’re developing knowledge of technologies at the intersection of computation, molecular biology and genomics, and applying those technologies to improve cancer diagnostics.”

One area of particular interest for Murtaza is circulating tumor DNA (ctDNA). These are fragments of DNA shed by a tumor into a patient’s bloodstream. Because they carry the same genetic alterations as the tumor itself, they offer clues about a patient’s specific cancerous mutations. That’s beneficial in the growing field of precision medicine, which seeks to offer patients the best treatments for their specific mutations.

Circulating tumor DNA is also much easier to access than the tumor itself. A simple blood draw, known as a “liquid biopsy,” can turn up these cells. As opposed to a traditional biopsy, a liquid biopsy can be performed multiple times in multiple spots in a short amount of time. This is useful to oncologists as they measure the spread of disease or the effectiveness of a treatment.

However, previously developed liquid biopsies have struggled to achieve the sensitivity and precision of a standard tissue biopsy, sometimes leading to inaccurate results. So Murtaza wanted push the limit of detection for liquid biopsies, especially for early stage cancer patients.    

While at TGen, Murtaza’s lab developed a liquid biopsy test known as TARDIS – that’s TARgeted DIgital Sequencing. Think of it as a personalized cancer test capable of detecting incredibly small amounts of cancer in a patient’s bloodstream.

The first clinical test for TARDIS involved early stage breast cancer patients who had received pre-surgical treatment, such as chemotherapy. Historically, it’s been hard to fully measure disease progression and treatment effectiveness in early stage cancer, which can lead to the under-treatment or even over-treatment of patients.

In this study, TARDIS looked for minimal residual disease, or MRD, left behind in the blood after these patients’ initial treatment. As outlined in a 2019 paper, TARDIS was able to detect ctDNA as low as 2 parts per 100,000 in the blood of these patients, making it one of the most sensitive liquid biopsies ever developed.

With proof of concept in hand, Murtaza is currently working on expanding that study to additional patients. But he also has plans to go bigger with this approach. “We are hoping to set up additional studies at the UW Carbone Canter Center to expand the application of this work into pancreatic cancer, rectal cancer and other areas where similar clinical challenges exist,” he said.

All of this could translate to more personalized treatment approaches to each patient’s individual cancer, a goal shared by UW Carbone’s Precision Medicine Molecular Tumor Board. Murtaza hopes assays like TARDIS can complement and build upon the work already happening there.

“Instead of just using a single blood sample or tumor sample, we could use multiple samples taken before, during and after therapy to see how patients are responding and if they have progressed on one round of therapy,” he said. “With that real time look into the patient’s cancer genome, we could potentially use that information to adapt each patient’s treatment plan and individualize it. That would be the goal.”

And while TARDIS is a major step forward for precision medicine, Murtaza’s not stopping there. Going forward, he hopes to pursue wider genome analysis strategies aimed at flagging potentially cancerous DNA before a tumor or malignancy clearly presents itself – something that could be a game changer.

“These approaches are a lot more tumor-independent, and therefore, much more applicable to questions of early detection,” Murtaza said. “If we look at blood samples, can we find out if there is any evidence of unexpected DNA that’s from potentially a cancer? That way, we could identify patients who may need more surveillance.”