ctDNA testing

Circulating tumour DNA (ctDNA) testing is a relatively recent advance in diagnostic technology based on the natural tumour lifecycle. As tumour cells grow and spread, dying tumour cells may release small pieces of their DNA into the bloodstream.1,2 This DNA circulates throughout the body, carrying the tumour’s genetic markers. Tests can now identify and analyse this DNA for genetic mutations just by obtaining a blood sample.3 This exciting new technology offers an important alternative to biopsies, which are the traditional method of mutation testing and require the invasive removal of tissues or cells from the part of the body with the tumour.3

There are many known genetic mutations in lung cancer, and a number of cancer treatments are targeted at these mutations to try to halt tumour growth.4 A biopsy or plasma ctDNA test helps physicians learn about the genetic makeup of lung cancer cells through a process called molecular testing.5,6 Molecular tests can detect recognised genetic mutations present in the cancer cells to help determine the best therapy for each patient.

Diagnostic testing may be necessary at multiple stages throughout the treatment process beyond just initial diagnosis.7 Lung cancer cells change over time and can gain new mutations that make them less responsive to initial treatment;8 as a result, further screening is often necessary to identify the specific changes and establish a new treatment plan.

When patients have to take a biopsy each time their cancer evolves, they are subjected to an often inconvenient and sometimes difficult process; in some cases, the tumour cannot even be biopsied.3 Taking a blood sample to examine ctDNA may provide a more rapid and less invasive way to screen tumours for newly acquired mutations and determine which targeted therapy may be suitable as a future treatment.6 It is important to note, however, that ctDNA mutation testing is associated with a false negative risk. As such, if a negative result is obtained this finding should be confirmed by testing a tumour sample, if it can be obtained.3

The ability to map tumour mutations at all stages of the disease may only improve our understanding of how tumours evolve, but may also hugely improve targeted therapy, by matching the correct patient to the correct treatment. This latest development in testing, coupled with the new treatments that are emerging, has the potential to change the course of lung cancer treatment over the coming years.


1 Diaz LA Jr, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol. 2014;32(6):579-586.

2 Kimura H, Kasahara K, Kawaishi M, et al. Detection of epidermal growth factor receptor mutations in serum as a predictor of the response to gefitinib in patients with non-small-cell lung cancer. Clin Cancer Res. 2006;12(13):3915-3921.

3 Thress KS, Brant R, Carr TH, et al. EGFR mutation detection in ctDNA from NSCLC patient plasma: A cross-platform comparison of leading technologies to support the clinical development of AZD9291. Lung Cancer. 2015; pii: S0169-5002(15)30073-8.

4 Langer CJ et al. Epidermal Growth Factor Receptor Inhibition in Mutation-Positive Non-Small-Cell Lung Cancer: Is Afatinib Better or Simply Newer? Journal of Clinical Oncology. 2013;31(27);3303-3305

5 Cancer Research UK. Lung cancer tests. Available at: http://www.cancerresearchuk.org/about-cancer/type/lung-cancer/diagnosis/lung-cancer-tests. Accessed April 2016

6 Yong E. Cancer biomarkers: Written in blood. Nature. 2014;511(7511):524-526.

7 Sui X et al. Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment. Cell Death Dis. 2013:4(10): e838

8 Yu HA, et al. Analysis of tumor specimens at the time of acrquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res. 2013;18:2240-2247

ATLAS ID: 965,602.011
Date of next review: March 2017