Circulating tumor DNA as a biomarker in KRAS G12C mutated non-small cell lung cancer patients

Master’s project

Anne Nørholm, BSc

I am currently doing my master’s thesis in molecular medicine. My project focuses on the analysis of ctDNA in KRAS (G12C) mutated lung cancer patients treated with the current standard treatment, and identification of predictive biomarkers for these patients when treated with sotorasib. Sotorasib was the first selective KRAS inhibitor to be approved for treatment in 2021 by the FDA. However, not all patients benefit from treatment, and no biomarkers for identifying these patients exist.

The overall goal is to investigate the dynamics of ctDNA levels, and how co-occurring mutations, other than KRAS G12C, and their expression, affect the efficacy of treatment with sotorasib. ctDNA from blood samples at baseline, week 2, week 4 and progression will be analyzed through next-generation sequencing (NGS) to investigate the mutational patterns of these patients. Furthermore, tumor gene expression will be analyzed through cell-free chromatin immunoprecipitation (cfChIP) and analysis of the ctDNA fragment length. Studies have shown that cfChIP and the fragment length of ctDNA differ between transcriptionally active and inactive genes and may therefore provide information about gene expression.