Liquid Biopsies for Cancer Detection

In 1970, only half of U.S. cancer patients lived another five years after diagnosis. Today, that number is 70 percent and rising and cancer deaths have declined by one-third since 1991. 

There are many reasons for these advances, but one crucial factor is that we are finding cancer earlier than ever. One promising contributor is the emergence of liquid biopsies, which aim to identify cancer signatures at very early stages. 

The first generation of liquid biopsies looked for mutations typically found in cancer, such as small changes in DNA, duplicated or deleted genes, or rearranged chromosomes. To do this, biomedical engineers had to develop a variety of techniques to read the miniscule quantities of mutations found in the bloodstream. 

Still, biopsies often missed the signs of early cancers, which are small and release few DNA fragments. They work less well on older people because their cells undergo natural mutations. Also, they target only known mutations and cannot pinpoint a cancer's location. 

This spurred biomedical engineers to develop new biopsies. One, methylation, involves the methyl groups that control DNA behavior. Each type of tissue has a unique methyl group signature. This persists even when cancer adds methyl groups that silence genes involved in normal immune responses. As a result, methylation groups can pinpoint where the cancer originated. 

Another emerging technology is fragmentomics. Ordinarily, the body chops the DNA of dead cells into fragments. Fragments from different organs and tissues have characteristic lengths, chemistries, and "footprints" created when DNA is wrapped up for storage. When cancer cells attack, they disrupt the storage architecture. This is enough to indicate their presence but still leaves markers that show where the cancer came from.

Both types of tests are highly sensitive to early cancers and many are under development. One commercially available test now screens for a signal shared by more than 50 types of cancer from a single blood sample. When combined with AI analysis, liquid biopsies promise earlier--and more successful--cancer detection than ever.