For decades, scientists have known about circulating tumor DNA, tiny amounts of DNA shed by dead tumor cells that float in the bloodstream, but haven’t been able to make good use of it — until now.
“I first read an article about circulating tumor DNA, and then I heard a lecture about it when I was still in training,” recalls Abhijit Patel, MD, PhD, now a radiation oncologist at the Yale Cancer Center. “Not much was really happening in the field at the time, but I had been intrigued by the idea ever since. Small tumors that do not produce any symptoms can shed circulating tumor DNA. So, if you could figure out a way to test for minuscule amounts of the circulating tumor DNA with high accuracy, you might be able to develop a test for early cancer detection.”
After accepting a faculty position at Yale University, Dr. Patel was establishing his lab and considering the possible directions for his research. At the time, his lab was focused on other projects, but Yale had just invested in state-of-the-art DNA sequencing technologies that he realized could be leveraged to develop methods sensitive enough to detect rare circulating tumor DNA molecules amid an excess of normal DNA found in blood.
Dr. Patel had an idea to tweak existing technology and develop a test that was sensitive enough to find circulating tumor DNA in patient samples. He started small. He recruited a few patients from his own clinic, and found some healthy volunteers to donate blood samples. After putting together a rough version of his idea, he tested the samples. To his astonishment and delight, his rudimentary technique worked. He could detect the circulating tumor DNA in patients undergoing treatment for lung cancer.
“A key challenge in developing blood tests for early cancer detection has been keeping false-positive results low, to avoid unnecessary follow-up testing and anxiety among people who do not have cancer. The promise of circulating tumor DNA as a tool for early cancer detection lies in its exquisite specificity. The circulating tumor DNA harbors genetic signatures that should not be found in healthy people, so false-positive test results are expected to be rare. If the test could be made sensitive enough and cheap enough, we could screen people regularly and find cancers early while the probability of cure is still very high.”
As a junior researcher who was still establishing his career, Dr. Patel didn’t have the funding to continue refining this early-detection technique for lung cancer. He also knew that he wouldn’t receive federal funding for research that was still in its infancy, so he applied for and was awarded a research grant from LUNGevity Foundation.
“The grant has been invaluable,” notes Dr. Patel. “It allowed us to refine the technique and to gather enough data to earn a large federal grant. Securing federal funding was key in helping to establish my laboratory and continue my lung cancer research.”
With the technology further optimized, Dr. Patel and his collaborators are gearing up for the next phase of their research: validating their technique by testing it on a larger number of blood samples obtained from patients with early-stage lung cancer.
Dr. Patel is not the only one excited about using circulating tumor DNA to detect cancer early. Several other labs are pursuing similar research, and biotech companies are attracting wealthy investors to enable large-scale clinical studies.
“It’s exciting,” says Dr. Patel, “to be able to contribute to this research, which has the potential to profoundly impact the way that cancer is diagnosed. More studies are needed before such a DNA-based blood test could be widely used for cancer screening, but I am hopeful that we will see this happen in the near future.”
Juhi Kunde, MA, is a science writer for LUNGevity. 