A collaborative team of researchers from the Translational Genomics Research Institute (TGen), Mayo Clinic, and Cancer Research UK Cambridge Institute (CRUK) have successfully shown that circulating tumor DNA (ctDNA), shed into the blood stream from cancer cells, can be used to track the progression of cancers and their response to treatment, in real time.
The researchers were able to obtain samples over a three year period from a patient with invasive ductal carcinoma—which had metastasized to other parts of her body. Using these samples the investigators were able to perform extensive analyses and comparisons between traditional biopsy results and those from ctDNA obtained through liquid biopsy methods.
“When patients receive therapy for advanced cancers, not all parts of the tumor respond equally, but it has been difficult to study this phenomenon because it is not practical to perform multiple, repeated tissue biopsies,” explained co-lead author Muhammed Murtaza, M.D. Ph.D., co-director of TGen’s Center for Noninvasive Diagnostics
The results of the study found that the DNA from the blood samples correlated with DNA from the traditional biopsies, reflecting the same pattern and timing of genetic changes as the cancer developed and responded to treatment. The results provide the first proof-of-principle that analyzing tumor DNA in the blood can accurately monitor cancer within the body.
“This definitively shows that we can use blood-based DNA tests to track the progress of cancer in real time,” noted co-senior author Carlos Caldas, M.D., senior group leader at CRUK. “The findings could change the way we monitor patients, and may be especially important for people with cancers that are difficult to reach, as taking a biopsy can sometimes be quite an invasive procedure.”
Dr. Murtaza added that “our findings empirically show that ctDNA analysis from blood samples allows us to detect cancer mutations from multiple different tumor sites within a patient and track how each of them responds.”
The findings from this study were recently published in Nature Communications through an article entitled “Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer.”
Additionally, the results from this study suggest that precise and real-time genetic monitoring of changes in a patient's cancer, through ctDNA analysis, could help inform physicians about the type of targeted treatment that might be best at each stage of the disease.
“The potential of using circulating DNA for estimating just how well a patient may respond to targeted therapies and for tracking the development of resistant clones in real-time, heralds a new era for precision medicine,” said Keith Stewart, M.B., Ch.B. director of the Mayo Clinic Center for Individualized Medicine, who was not directly involved in the research.
While this study was done in a single patient with a specific type of cancer, the implications from the data the authors obtained may have an invaluable impact on future studies using ctDNA
“We were able to use the blood tests to map out the disease as it progressed. We now need to see if this works in more patients and other cancer types, but this is an exciting first step,” stated Dr. Caldas.
“Spotting tumor DNA in the bloodstream is a promising area of research, and has the potential to give doctors valuable clues about a patient's disease without having to take repeated tumor samples,” remarked Kat Arney, Ph.D., science information manager at CRUK. “For now, surgical biopsies still play an important role in diagnosing and monitoring cancers. But this work gives us a window into the future, where we'll use less invasive techniques to track the disease in real time.”