It’s a lot to ask of a run-of-the-mill blood draw, but Curtis and her group are devising a search tactic that goes beyond identifying rare mutations in DNA. She’s looking at epigenomic footprints, types of markers typically embedded in DNA. While these markers are often found enclosed in the cell, Curtis takes advantage of cell-free DNA, which floats openly in the bloodstream after shedding from a tumor or from healthy tissues.
“We’re taking a really different approach. We leverage epigenomic profiles, which contain information about which tissue the cell-free DNA is derived from and if it’s cancerous,” Curtis said. “And while certain mutations are important hallmarks of cancer, there’s a unique profile that the epigenome provides, including clues about the cell’s activity or state.”
Research from Curtis’ lab shows that some cancers are simply born to be bad. That is, from day one, mutations and epigenomic factors render the cancerous cells aggressive, malignant and more lethal overall. One day, Curtis hopes, a blood-based analysis could detect that kind of aggressive cancer and its point of origination, all before the patient even shows symptoms. In that sense, it would work as a screen, she posits, that everyone could incorporate into their routine annual checkup.
That’s still a long time away, Curtis said. But in her research, she’s beginning to apply the blood-based technique to consenting cancer patients, working backward to test her technology’s ability to pinpoint cancer types and aberrant signaling from cell-free DNA. So far, their preliminary research has yielded robust results.
“A big part of the challenge is that cell-free DNA in and of itself hasn’t been deeply studied yet. What we’re looking for here are really needles in haystacks — rare molecules that have been shed from somewhere in the body,” Curtis said. “There’s still a question surrounding what the makeup of a healthy individual looks like, so we’re working on understanding that too, because without that, we have no meaningful reference.”
The future of PHIND
Technology, however, can advanceonly as far as researchers’ understanding of biology enables it. “The smart toilet, which is being developed in my lab, can’t work miracles if it doesn’t know what to look for in the urine. It’s not a crystal ball; it has to know what biomarker(s) to detect,” said Gambhir, the Virginia and D.K. Ludwig Professor for Clinical Investigation in Cancer Research. “That’s why we need more people on the basic biology side to understand the early changes as cells transition from normal to ill cells.”
To this end, PHIND has so far doled out $2.75 million to help catalyze basic, prevention-focused research at Stanford based on a competitive formal process. There were some 20 projects funded in the initial round. Earlier this month, the center officially announced the availability of an additional $1.5 million in seed funding. The goal is to launch up to 12 new research projects by the end of this year.
“Science isn’t often discovery out of nowhere. It comes out of fortuitous collisions, in which different fields that don’t typically communicate come together,” Gambhir said. “And that’s what we want to facilitate with PHIND to empower the science behind precision health and earlier diagnostics of multiple types.”