Liquid biopsies support precision medicine

The treatment of cancer patients with therapies that are specifically targeted to their cancer is a major goal of precision medicine and may lead to significantly improved clinical outcomes.

The first step in providing a specifically targeted therapy is the analysis of a patient’s tumour. This allows the tumour to be classified according to the cancer mutations that are present within the cells of the tumour. The patient can then be treated with a therapy that is known to be effective against tumours of the same classification.

Conventionally, a patient’s tumour is analysed by obtaining a tumour biopsy and then sequencing the DNA of tumour cells in the biopsy to identify the presence of cancer mutations. However, taking a biopsy from a tumour is a significant and invasive procedure that cannot be repeated regularly. This is problematic for therapies that are specifically targeted to a patient because the tumour cells of the patient may acquire cancer mutations over time that were not present when the original tumour biopsy was taken. Mutations within the ESR1, HER1 and AKT1 genes for example are frequently acquired by tumours in their advanced stages. As the cancer mutations within a tumour change, the most effective therapy to treat that tumour may also change, and an initial therapy selected according to cancer mutations identified in the original tumour biopsy may no longer be effective for later stages of the same tumour. If the cancer mutations present within a tumour could be assessed more frequently over time, the therapy that is selected to specifically target the tumour may be continually adapted and optimised as the cancer mutations within the tumour change. This would be a significant advance in cancer care.

A potential solution to this problem is the use of liquid biopsies. Whilst it is more normally associated within the nucleus and mitochondria of cells, DNA is also found in the blood plasma in the form of circulating free DNA (cfDNA). In cancer patients, some of this circulating free DNA originates from tumour cells. This subset of the circulating free DNA is known as circulating tumour DNA or ctDNA. Since it originates from tumour cells, ctDNA contains the same mutations as the patient’s tumour, so the mutations that are present in the tumour can in principle be identified by isolating and sequencing the ctDNA from a sample of plasma (a so called “liquid biopsy”). Plasma samples are minimally invasive and can be taken throughout a patient’s treatment, allowing the therapy used to treat the patient to be adapted to the genetic changes that occur within a tumour as it develops and responds to treatment. However, the feasibility of replacing tissue biopsies with liquid biopsies as a means to inform the choice of targeted cancer therapy has not yet been established in clinical trials.

The publication of initial results from a clinical trial designed to compare liquid and tumour biopsies in advanced breast cancer patients represents a step towards achieving this goal.

In this clinical trial, rare mutations within certain cancer genes were identified by ctDNA analysis and used to divide breast cancer patients into different cohorts. Each cohort was then treated with a different cancer therapy, according to the cancer mutations present in that cohort. The trial found that ctDNA analysis displayed similar accuracy and sensitivity to conventional tumour biopsy analysis and was just as effective at identifying patients for targeted therapy. ctDNA analysis was also quicker and could be performed on a higher proportion of breast cancer patients.

These findings show that the analysis of ctDNA in liquid biopsies may be a rapid and effective means for screening for the presence of cancer mutations which may then inform individualised approaches to patient treatment.

This is likely to encourage the more widespread use of precision medicine techniques in oncology. As their advantages are recognised, the commercial value of ctDNA analysis tools will grow and IP protection will become an increasingly important issue for businesses seeking to develop assets in this field. The complex combinations of biology and information processing that lie at the heart of ctDNA analysis will present challenges to patent practitioners and a considered and forward-looking IP strategy will be important in protecting these assets.