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Article • Mutated DNA in blood

Liquid biopsy detects tumour changes in real time

New findings from a scientific collaboration between the German Cancer Research Centre (DKFZ), the National Centre for Tumour Diseases (NCT) Heidelberg and the Thoraxklinik Heidelberg suggest liquid biopsy as a promising tool to monitor lung cancer patient tumours early. Scientists associated liquid biopsy readouts with clinical data and could track tumour responses to cancer drugs in real-time.

Although currently  considered the ‘gold standard’, tissue biopsies are not without  limitations. Thus, in recent years, a new alternative, liquid biopsy,  has gained attention. When cells die, they release their DNA (so-called  cell free DNA, cfDNA) into the bloodstream. For tumour cells that die  after therapy, the cfDNA contains mutations that could be detected and  analysed with PCR or sequencing tools for non-invasive diagnosis.

However, the sensitivity and clinical information  provided by liquid biopsy is less clear, prompting the group to  investigate further. By collaborating with partners at the Heidelberg  Thoraxklinik, the DKFZ researchers recruited a focused cohort of 16 lung  cancer patients, all carrying prominent mutations, and were undergoing  tyrosine kinase inhibitor (TKI) treatment. Over a period of up to two  years, the researchers collected sequential blood plasma samples from  each patient and extracted the DNA.

By analysing the data, the scientists made three  interesting observations.  First, the number of mutated alleles in  patients changed according to the clinical course of the disease. For  example, in one patient, the initiation of TKI therapy was paralleled by  a drastic and immediate (within 26 hours) rise of mutated cfDNA in the  blood plasma, probably indicative of an effective therapy response that  resulted in many cancer cell deaths. Interestingly, this ‘peak’ declined  shortly afterwards, suggesting that TKI therapy had its greatest impact  only during the first few days of treatment. 

Secondly, the researchers found that low, or  absent levels of mutated cfDNA associated with sustained periods where  the disease remained under control and the tumour did not grow. Finally,  in patients whose tumour relapsed and who died soon afterwards, the  mutated cfDNA levels were found to be increasing rapidly over short  timeframes.

These findings highlight liquid biopsy’s  sensitivity in detecting and reflecting tumour changes in real time,  while providing the advantages of being less invasive. The molecular  data provided by this method might also help inform physicians to make  earlier decisions on therapeutic strategies.

04.08.2017

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