Predicting Cancer Progression With Methylation Levels In Blood cfDNA

Pixabay License | Source:  Pete Linforth , no changes made.
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Oncologists and their patients need to understand the response to treatment earlier and with more accuracy than is currently possible by imaging (CT, PET/CT, MRI) after approximately three months of treatment. As tumours release free DNA into the blood stream one possible alternative method to monitor cancer progression, or regression, is through serial “liquid biopsies” and analysis of the cell free DNA (cfDNA). This is the approach Lexent Bio is developing.

Founded in 2015, based in San Francisco, California, Lexent Bio is building novel liquid biopsy technology to change the way cancer is treated. Notably the company’s cfDNA methylation status approach is focused on monitoring cancer treatment response, rather than diagnosis.

DNA can be epigenetically modified by methylation, changes of which are linked to cancer pathogenesis and progression. Lexent Bio recently presented a study at the 2019 ASCO Annual Meeting, the aim of which was to determine if changes in cfDNA methylation patterns before and after initiation of cancer treatment could predict outcomes prior to routine imaging and clinical follow-up.

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Clinical data and blood was prospectively collected from 28 patients with metastatic malignancies (13 lung, 11 breast, 4 other). Blood was drawn prior to the start of a new treatment, after first cycle, and/or second cycle. Whole-genome (WG) bisulfite sequencing on plasma cfDNA was performed to determine methylation levels. This was compared with methylation levels from healthy individuals.

The sensitivity of the assay for identifying progression was 78% and the specificity was 95%. The researchers concluded that the results showed that whole-genome cfDNA methylation changes are a novel signature with potential to identify patients whose treatment regimen is ineffective, well before a conclusion from imaging is feasible. It is thought that integrating methylation-based changes with genomic alterations will increase the performance of cfDNA-based cancer progression assays.