New Personalized Blood Test Monitors Success Of Cancer Therapies
Virtually all cancers arise through mutation of genes that control cell growth. As the cancers grow, they shed fragments of DNA, biological evidence of these mutant genes, into the bloodstream. Now, Johns Hopkins Kimmel Cancer Center researchers have developed a novel test to measure tumor-derived DNA in the bloodstream.
The researchers say the blood test, based on the unique genetic fingerprint contained within the genome of every cancer, can not only detect the presence of tumor but track its progress. The results of this proof-of-concept study are reported in the September 2008 issue of Nature Medicin, and have been made available in advance at www.nature.com/nm.
“Just as DNA has been used to detect, measure and manage chronic viral infections, like HIV, measuring circulating tumor DNA could similarly enhance the management of cancer,” says Luis Diaz, M.D., assistant professor of oncology, who led study.
Every cancer has a set of mutated genes that are present in cancer cells but not in normal cells. In tumor tissue from a group of 18 patients with colorectal cancer, Diaz and colleagues identified the mutations present in each patient’s cancer. With this information, they then used a method known as BEAMing (beads, emulsion, amplification, magnetics) to search for corresponding mutant tumor DNA in plasma from these patients. In all 18 cases, the corresponding mutations found in the tissue were also detected in the plasma. Their test not only detected the mutant genes but measured the level of circulating tumor DNA, providing molecular evidence of patients’ tumor burden. Higher levels of circulating tumor DNA translated to more disease. “Beyond simple detection, using this new approach we can now monitor tumor burden in real time using the mutations that actually caused the disease,” says Frank Diehl, Ph.D., lead author of the study.
“One of the most interesting findings is that circulating tumor DNA may have the sensitivity to measure minimally residual disease that is not evident in X-rays or CT scans, “ says co-author and surgeon Michael Choti, M.D.
Patients enrolled in the study underwent potentially curative surgery and were followed for up to two years. After surgery, circulating tumor DNA was detected in all patients whose disease eventually recurred, often as soon as one day after surgery and months before it was visible in X-rays or CT scans. Those patients whose mutant DNA levels fell to undetectable levels after surgery remained disease-free.
The test is still being studied and is not yet available in the clinic, however, Diaz says, “One clinical application may be the detection of residual disease after curative surgery.” “We know that not all patients need intensive adjuvant chemotherapy, and this test could help us decide who would benefit.”
While these studies were done on colorectal cancers, Diaz says the test could be applied to any cancer that is linked to a known gene mutation.
In addition to Diehl, Kerstin Schmidt, M.D., was a co-lead author of this study, and co-authors included Michael A. Choti, M.D., Katharine Romans, M.S., Steven Goodman, M.D., Ph.D., Meng Li, M.D., Katherine Thornton, M.D., Nishant Agrawal, M.D., Lori Sokoll, Ph.D., Steve A. Szabo, B.S., Kenneth W. Kinzler, Ph.D., and Bert Vogelstein, M.D.
The research was funded by the Howard Hughes Medical institute, the Virginia and D.K. Ludwig Fund for Cancer Research, the Miracle Foundation, the National Colorectal Cancer Research Alliance and the National Institutes of Health.