How does early detection work?
Like many diseases, cancer treatment works better and survival rates increase the earlier the cancer is detected. Traditional methods of tumor detection, such as MRI and mammograms, are reliable, but typically require patients to be in an advanced stage
of cancer development. Blood screening, also called liquid biopsy, is an advanced method of early detection that uses circulating tumor DNA (ctDNA) to directly measure cancer DNA. Tumors that are too small to detect manually shed nucleic acids, also
called cell-free DNA (cfDNA), into the patient’s blood. Genetic signatures from the tumor can be detected through next generation sequencing (NGS) of the DNA extracted from the patient’s blood. Deep sequencing of this DNA enables detection
of cancer mutations at low levels in the blood. Since the tumors are still very small, liquid biopsy enables asymptomatic screening before the patient has cancer symptoms and is a noninvasive testing method of finding cancer at the early stages.
To prevent patient discomfort, the blood taken from a patient to perform liquid biopsy is very small. Consequently, the amount of cfDNA on which to perform sequencing is limited. Sequencing technologies must be extremely efficient to take advantage of
the precious samples. Next generation sequencing has 3 main steps: library prep, sequencing, and analysis. During the library preparation step, DNA is converted into libraries, which allow the sample to be sequenced. Sensitivity to tumor detection
can be increased by a high conversion rate of DNA to library during the library preparation step. This allows NGS to detect low-frequency variants.
Error correction and accuracy can be further enhanced through the use of unique molecular identifiers (UMIs). UMIs are short sequences, often with degenerate bases, that incorporate a unique barcode onto each molecule within a given sample library. UMIs
have been shown to reduce the rate of false-positive variant calls and increase sensitivity of variant detection. By incorporating individual barcodes on each original DNA fragment, variant alleles present in the original sample (true variants) can
be distinguished from errors introduced during library preparation, target enrichment, or sequencing. Any identified errors can be removed by bioinformatics methods before final data analysis.
Early cancer screens contribute to cancer research by providing information about cancer development. As cancer is detected earlier, treatments can be developed to target mechanisms of tumor development. Early treatment targets may eventually be used
to develop cancer preventions.
The same techniques used for early detection can also be used after a patient is in remission. During or after treatment, a small number of cancer cells usually remain in the patient’s blood, called minimal residual disease (MRD), and can lead to
relapse. Liquid biopsy and NGS can detect minute numbers of cancer cells and determine whether the treatment has completely eradicated the cancer. MRD detected by liquid biopsy can also be used to track the efficacy of treatment and adjust the therapy
the patient is receiving.