ctDNA in cancer care
Elza de Bruin
Director Translational Medicine, AstraZeneca, Cambridge, UK
Circulating tumour DNA (ctDNA) offers a unique possibility to identify and track tumour-derived mutations in a minimal invasive manner, opening the possibility to optimise cancer care. During her seminar, Dr. Elza de Bruin will discuss three approaches of how ctDNA analyses can inform and optimise treatment of cancer patients. The first approach is the identification of subclonal EGFR T790M mutations, driving resistance to first and second generation EGFR TKI in lung cancer, in patients from the AURA-3 clinical trial. Patients with subclonal T790M mutations had a worse response to Osimertinib and further analyses was performed to understand potential mechanisms of resistance. A next approach is the identification of co-occurring mutation in genes used as biomarker for patient selection. Analyses of samples collected in the SELECT-1 study identified co-occurring mutations in up to 8% of non-small cell lung cancer patient with a positive test for KRAS 34G>T (encoding the G12C variant), with 35G>T the most frequently co-occurring variant, translating to either G12F or a G12C&G12V double mutant, negatively impacting responses to KRAS G12C-specific inhibitors. The last approach is the potential use of ctDNA detection itself to identify patients with a high risk of relapse earlier than through conventional imaging approaches. Proof of concepts studies in breast cancer patients revealed that ctDNA was detectable using novel highly sensitive tumour-informed ctDNA assays in almost all patients prior to disease relapse, offering a window for earlier treatment intervention.