An extraordinarily sensitive new blood test has been developed that promises to be able to effectively track the progression of breast cancer at its earliest stages. It is suggested the blood test could track the efficacy of drug therapies better than current imaging techniques and prevent unnecessary surgical procedures or needless extra doses of chemotherapy.
It can be quite tricky catching cancer through simple blood tests. A variety of different biomarkers have recently been raised as potentially useful, from identifying certain RNA profiles in blood platelets to detecting signs of a process called protein phosphorylation. One of the more promising techniques being explored is the detection of fragments of tumor DNA that can circulate through person's bloodstream.
These tiny cancerous traces are called ctDNA, and one of the biggest challenges faced in developing an accurate ctDNA blood test is producing a test sensitive enough to detect these fragments that often only appear in extraordinarily low levels, especially in the early stages of disease before a cancer has metastasized.
The new method, reported in the journal Science Translational Medicine, is called TARDIS (TARgeted DIgital Sequencing), and it is claimed to be almost 100 times more sensitive than existing ctDNA blood tests. One of the key innovations in the TARDIS method is that it takes samples of an individual patient's tumor and personalizes the test to detect the specific mutations associated with that cancer.
"Fragments of ctDNA shed into blood by tumors carry the same cancer-specific mutations as the tumor cells, giving us a way to measure the tumor," explains Bradon McDonald, the study's first author. "The problem is that ctDNA levels can be so low in non-metastatic cancer patients, there are often just not enough fragments of ctDNA in a single blood sample to reliably detect any one mutation. This is especially true in the residual disease setting, when there is no obvious tumor left during or after treatment. So, instead of focusing on a single mutation from every patient, we decided to integrate the results of dozens of mutations from each patient."
At this stage the method is not geared towards being an initial diagnostic tool, as it requires a tumor biopsy, but its remarkable sensitivity offers doctors amazing new ways to track how effective a given treatment is progressing. It's suggested around 30 percent of patients unnecessarily embark upon surgery following initial drug therapy as current imaging techniques are not detailed enough.
"This could be a game-changer," says Carlos Caldas, from Cancer Research UK Cambridge Centre. "Instead of patients undergoing six to eight cycles of chemotherapy (15-21 weeks of treatment), after one or two cycles (3-6 weeks) we would use the TARDIS test to look for a significant drop in circulating tumor DNA. If a drop was not detected, the treatment could be stopped or changed."
Early studies proving the efficacy of TARDIS have been incredibly promising. One validation study examining 33 women with early-stage, or advanced but pre-metastatic breast cancer revealed the test as able to identify ctDNA traces in 100 percent of subjects. The next step for the research is to conduct a larger human trial, to validate the test and also better understand what concentrations of ctDNA can indicate whether a treatment has been successful.
The new research has been published in the journal Science Translational Medicine.
Source: Cancer Research UK
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