Scientists from a number of institutions, including the John Hopkins Kimmel Cancer Center and the University of Texas Southwestern Medical Center, have found a promising new way to non-invasively screen for early-stage cancers using tiny fragments of DNA shed by tumors into the bloodstream. These circulating tumor DNA (ctDNA) strands were detected in more than 75% of patients studied by the team. The study consisted of 640 patients with various types of cancer, and the cancers that most often presented ctDNA (quantitated by polymerase chain reaction) were advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, liver, head, and neck. Half of patients with primary brain, renal, prostate, or thyroid cancers had identifiable ctDNA. ctDNA was even found in patients without detectable circulating tumor cells, implying that the incidence of the two events are not mutual, but no cases of circulating tumor cells without ctDNA existed. “The most promising aspect is that ctDNA can identify early-stage cancers,” said Luis Diaz, M.D., from the Swim Across America Laboratory at Johns Hopkins.
As stated by the authors in Science Translational Medicine, ctDNA could be used as a “personalized biomarker” test and cancer screening tool. “We’re already very good at treating and curing cancer when it is localized,” said lead author Chetan Bettegowda, M.D., Ph.D. “But we wanted to develop a non-invasive technology to enhance detection of cancer at an early stage, and we feel this is an exciting starting point for further work using this method.” The use of ctDNA as a biomarker could even be used to predict what type of therapy would be most effective to treat the afflicted patient’s cancer. An analysis of tumors and blood samples from 206 different patients showed that 87% of patients’ ctDNA contained a KRAS gene mutation, indicating that epidermal growth factor receptor (EGFR) blockade therapy may be of benefit.
Further demonstrating the versatility of ctDNA biomarkers, the scientists also looked for mutations in ctDNA from 24 patients who objectively responded to EGFR blockade therapy but subsequently relapsed. They found that 23 patients had one or more mutations in genes involved in the mitogen-activated protein kinase (MAPK) pathway. This may elucidate way cancers build resistance to EGFR blockade therapy, as MAPK is involved in cell signaling to control gene expression and cell survival. Wrote the authors, “Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.”
The work was supported by The Lustgarten Foundation for Pancreatic Cancer Research; the Hilton Foundation; the Commonwealth Fund; Swim Across America; a Burroughs Wellcome Career Award for Medical Scientists; the Johns Hopkins Clinician Scientist Career Development Award; a Brain Science Institute Translational Research Grant; a Pediatric Brain Tumor Foundation Award; the Virginia and D.K. Ludwig Fund for Cancer Research; the National Institutes of Health; the European Community’s Seventh Framework Programme; the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; the American Association for Cancer Research Stand Up to Cancer – Dream Team Translational Cancer Research Grant; the Ballanger Trust; a Clinical Innovator Award from the Flight Attendant Medical Research Institute Fund; the Victorian Cancer Agency; the Sao Paulo Research Foundation; the Michael Rolfe Foundation; Dennis Troper and Susan Wojcicki; the Sol Goldman Pancreatic Cancer Research Center; and AIRC IG grants.