First applied to COVID-19
The longtime systems biologist first came up with the idea of a drug-matching platform during the early days of the COVID-19 pandemic. He focused first on a class of compounds known as kinase inhibitors and worked with a team of Fred Hutch infectious disease experts to identify and validate a handful of FDA-approved compounds capable of inhibiting inflammatory immune reactions certain COVID-19 patients faced.
But these represented only one class of drugs. He soon realized he could move beyond COVID — and the kinase pathway.
He partnered with Fred Hutch’s Pete Nelson, MD, who holds the Stuart and Molly Sloan Precision Oncology Institute Endowed Chair, to see if his machine learning-based drug screening platform could identify potential drugs that could be repurposed to help patients who’ve tapped out of all their metastatic prostate cancer treatments. Again, he produced matches.
“We’re looking at all kinds of drugs now,” Gujral said. “We’ve gone beyond kinase inhibitors — now it can be any drug.”
In addition to creating TRACER, the grant from the FDA will allow Gujral and his team to directly test drugs on tissues from various patients’ rare cancers.
But he’s not content with just finding drugs that can target rare cancers. Like most scientists, he wants to know why — exactly — these matched drugs work on the tumors.
“When we get these hits, we try to figure out why it works,” Gujral said. “These drugs are often built for one or two targets, but we know they target many other things. We’re going to test these drugs in mouse models with the same tumor as the patient so we know what it’s doing to make the tumor shrink. Having all that data and insight is valuable to understand the biology.”
He’s also developing valuable rare cancer tumor models.
So far, the team has produced and disseminated preclinical models of fibrolamellar cancer, ependymoma (a type of brain or spinal cord cancer) and epithelioid hemangioendothelioma, or EHE, a rare cancer in the cells that make up blood vessels. In days to come, the team plans to develop additional preclinical models including cell lines, organoids and PDXs.
Eric Holland, MD, PhD, senior vice president and director of Fred Hutch’s Human Biology Division, who holds the Endowed Chair in Cancer Biology and heads STTR, is enthusiastic about TRACER’s launch — and its mission.
“The Transformative Rare Cancer Research Initiative is an exciting opportunity for cross-collaboration within the current STTR tumor teams,” he said. “The team will build on existing partnerships, spark new collaborations and help build momentum for the rare cancer community.”
Additional funding needed
Solving the science and building and maintaining momentum is just part of it, though.
Gujral said there are many other challenges ahead for the TRACER team. Funding, he said, will be a major hurdle. Questions — specifically about whether a patient’s insurance will cover the cost of the analysis or any repurposed drugs found via the platform — will also need to be resolved.
But this leading-edge scientist remains optimistic about what he sees as a winning proposition.
“It’s in the interest of all the stakeholders, including the pharmaceutical and insurance companies, to expand the use of their drugs to expand their market size,” he said. “Once a drug is approved for one cancer, it’s in their interest to see if it will work in other indications and expand the profiles.”
“Pharma wins, insurance wins — and mainly, the patients win,” he said.