Developing a methylation-sensitive cfDNA assay
Supervisors
Trevor Graham
ICR, 1st supervisor
Chris Sale
Nonacus, 2nd supervisor
Objectives
Tracking clonal evolution during cancer treatment is essential for understanding resistance dynamics. DNA methylation, an epigenetic marker, remains stable in cell-free DNA (cfDNA) and provides an effective means to monitor tumour evolution. In collaboration with industrial partner Nonacus, this project aims to develop a methylation-sensitive cfDNA sequencing panel and computational tools to track tumour evolution in clinical trial cohorts, offering a low-cost, high-accuracy solution for real-time monitoring of resistance evolution.
Methodology
Specific objectives: • Develop a methylation-sensitive cfDNA sequencing panel in partnership with Nonacus for clinical application. • Create a computational framework to interpret these data, enabling accurate tracking of clonal evolution during treatment. • Apply cfDNA assays to monitor resistance evolution in clinical trial cohorts, validating efficacy in a real-world setting.
Expected Results
The project will produce a novel cfDNA assay and computational tools for tracking cancer evolution during treatment, enhancing the ability to monitor resistance in clinical settings. This partnership with Nonacus aims to bring an innovative, cost-effective solution to clinical oncology, improving real-time decision-making in cancer treatment.
Planned Secondments
CUT (Lakatos) in year 3 (2 months) to receive training on modelling and to coordinate efforts to track clonal evolution in patients.
BSC (Gabaldón) in year 3 (2 weeks) to get exposed to research on a supercomputing institute.
Enrolment in doctoral programs
Institute of Cancer Research, London, UK
References
https://www.nature.com/articles/s41467-025-59479-7
https://www.nature.com/articles/s43018-025-00955-w
https://www.nature.com/articles/s41586-024-07747-9
https://www.nature.com/articles/s41586-022-05311-x
https://www.nature.com/articles/s41586-022-05202-1