Can we use a simple blood test to detect cancer?

Breast cancer could be detected using a blood test, according to reports out today. Scientists at the Australian National University (ANU) are working with counterparts in France to make this form of cancer detection, that is far less invasive and expensive than other tests such as biopsies, a reality.

Researchers say they’ll be able to test for breast cancer in blood by checking the proportion of certain isotopes, carbon-13 and nitrogen-15 – which are variants of particular chemical elements – in a tissue sample. This can reveal whether the tissue is healthy or cancerous.

But the test is still around ten years away from being used in the clinic, although research in this area is booming. Scientists have been looking for, and finding, ways to track various cancers in blood for some time. Indeed, blood-based testing for solid tumours in not a new development.

Currently, some tests are used to detect proteins found in higher levels in certain types of cancer. These are called “tumour markers” and include CA15-3 in breast cancer, CA19-9 in pancreatic cancer and CA-125 in ovarian cancer.

However they are relatively unspecific. For instance, a person with ovarian cancer will have high levels of CA-125, but high levels don’t always mean the person has ovarian cancer. They could indicate a benign tumour on the ovary instead. Nor can these tests assess how the cancer changes over time. So how are the new blood tests being developed to hit the target?

First, a bit about cancer

Cancer is a disease of the genome, which means it’s characterised and caused by changes in our genes that can drive a healthy cell to mutate into a cancerous one.

Cancer remains difficult to treat because each cancer is different, even within the same cancer type, such as breast or bowel. Each tumour has a genetic code that makes it unique, but there are also genetic differences within the tumours themselves. And tumours can evolve over time to become resistant to treatment.

To better guide treatment strategies, every cancer case has to be evaluated independently and monitored for changes over time. With recent advances in cancer genetics, we can better understand the difference between cancer and normal cells and pinpoint where things have gone wrong.

When cancer cells rupture and die, they release their contents, including their DNA with their unique genetic code, into the bloodstream. This free-floating DNA is referred to as circulating tumour DNA (ctDNA).

Through development of refined techniques to measure and sequence this ctDNA in the bloodstream, scientists can get a snapshot of the cancer itself, which is referred as a “liquid biopsy”. Taken over time, such blood samples would show clinicians whether treatments are working and whether tumours are developing resistance.

This is like evaluating changes in household diets by screening rubbish bins. This can be done repeatedly without disturbing the privacy of family.

Liquid biopsies

Classical methods for monitoring cancer dynamics, such as tumour markers and scans to estimate tumour size, can’t assess the tumour’s genomic status.

Genetic analyses of a sample of the tumour, also referred as a biopsy, are becoming standard care in pathology departments. However, a biopsy only provides a snapshot of genomic changes on that particular piece of tumour. A biopsy also commonly requires an invasive surgical procedure, so cannot be performed frequently.

So if changes are occurring over time, decisions based on old results will be outdated. Better methods to study tumour evolution can greatly improve cancer care.

One of the most advanced examples of liquid biopsy application in cancer care is in the treatment of lung cancer. Researchers discovered that around 60% of lung cancers treated with a drug to target something called the epidermal growth factor receptor (EGFR) on cancer cells, become resistant to therapy. Then they found the culprit responsible for the resistance: a small change in the EGFR gene, known as T790M mutation.

Scientists were then able to devise a new drug to target T790M. So when patients develop resistance to the first therapy, they could be treated with this new drug.

In parallel, development of a test to detect this mutation in blood plasma or even urine ctDNA, allows for patients to be monitored and timely change of treatment to occur when resistance starts to show.

Our recent study showed that response to treatment can be tracked by measuring ctDNA in the blood of melanoma patients. A decrease in the amount of ctDNA accurately mirrored the shrinking of the cancer. But more importantly, increases in ctDNA indicated that the cancer was coming back.

This is important as it can expedite treatment change when the cancer is still under control and the patient’s health hasn’t been compromised. We could also detect the development of mutations that the melanoma acquired in its genes to become resistant to treatment. This can inform treatment strategies as more drugs become available for metastatic melanoma.

Other developments

In addition to ctDNA, there is intensive research of other blood components that can reveal what is going on in a patients’s cancer. These components include cancer cells that released into circulation, called circulating tumour cells or CTCs, small droplets released by the cancer called exosomes, and other types of genetic material and proteins.

A team of researchers at the Walter and Eliza Hall Institute showed recently that colon cancer patients with detectable ctDNA in the blood after the tumour was removed by surgery, are at high risk of the cancer coming back. Using such a test will identify these high-risk cases so the residual cancer can be removed.

The promises of what we can discover about the patient’s tumour from a simple blood sample are still scratching the surface. As this window widens, a better and more complex picture of the cancer emerges, empowering researchers and clinicians with more information to deploy the anti-cancer arsenal at their disposal.