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Breakthrough announced in circulating tumour cell research

Published on 18/06/21 at 09:26am

Liquid biopsy company, Angle, has announced results from their study in non-small cell lung cancer (NSCLC) which demonstrates the benefit of analysing circulating tumour cells (CTCs), in addition to circulating tumour DNA (ctDNA), to inform treatment decisions.

The aim of the study was to detect Epithelial Growth Factor Receptor (EGFR) mutations, a key target for therapy selection, in ctDNA and matched CTCs from a single blood sample. The trial used cell separation technology, Parsortix, to harvest CTCs in blood samples from 48 metastatic NSCLC patients, with known EGFR mutations, before treatment with a targeted therapy and again at disease progression.

Isolated CTCs were lysed and genomic DNA from the harvested CTCs was analysed using the company’s Crystal Digital PCR, a tool for detecting and quantifying gene mutations. CTC-derived DNA was analysed in 64 samples and the EGFR mutational status assessed before treatment and at disease progression.

Direct comparison of the CTC results with matched ctDNA results revealed significant differences in the patient’s mutational status on which the therapy decision is based.

Prof Evi Lianidou, Head of the Molecular Diagnostics Laboratory focused on Liquid Biopsy at the Department of Chemistry, National and Kapodistrian University of Athens, said: “CTCs, as living cells that are active in the metastatic process, can provide prospective insight into a patient’s cancer. In comparison, ctDNA derived mainly from dead and dying cells, provides important but historical information on a patient’s disease. The genetic and phenotypic diversity observed in CTCs most likely mirrors that of the patient’s tumour and is reflective of cell evolution under treatment induced selective pressure.”

The differences observed are believed to be clinically important since CTCs are living cells actively involved in metastatic evolution and spread. The heterogeneity observed in CTCs is reflective of cell evolution under treatment induced selective pressure and provides insight into cancer evolution.

Identifying the differences between mutations in ctDNA and CTCs in longitudinal studies could help guide therapy decisions and provide an important enhancement to monitoring patient response in cancer drug trials.

Angle Founder and Chief Executive, Andrew Newland, said: “This study, which analysed blood samples taken from patients during treatment, demonstrates the dynamic and heterogeneous nature of NSCLC and the need for analysis of CTCs as well as ctDNA from serial liquid biopsies to provide information on disease progression and drug resistance. Critically, this study supports the view that CTCs, rather than ctDNA, are key to gaining an insight into the future development of a patient’s cancer.”

Kat Jenkins

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