Metrology for molecular Measurable Residual Disease (MRD) testing in cancer and precision medicine

EU initiatives Mission on Cancer and Beating Cancer Plan highlighted that, in 2020, 2.7 million people were diagnosed with cancer in Europe, and 1.3 million died. Rates are expected to climb due to aging populations, unhealthy living, or lack of access to early screening. Following treatment, cancers can return and be missed at early stages by conventional image-based screening. Catching relapses quickly is crucial as it provides a wider range of treatment plans for patients. Molecular Measurable (or Minimal) Residual Disease (MRD) testing offers superior remission monitoring but is not yet standardised, leading to incomparable data, barriers to regulatory qualification, and wider clinical adoption.

Building on the work of GenomeMET, using molecular techniques such as digital PCR (dPCR), the project will establish a  Reference Measurement System for haematological cancers, targeting a sensitivity at or below current thresholds (e.g. mutant: reference gene ratios 1:10^-3 to 1:10^-5). It will also develop a new candidate World Health Organization (WHO) SI-traceable reference material for Amyloid Leukaemia. Solid tumours will also be addressed using dPCR, Next Generation Sequencing and AI models for liquid biopsy measurements. Both approaches will be validated by interlaboratory comparisons with the aim of developing test kits and procedures for MRD that address limit of detection, quantification, and measurement uncertainty.

Standardised, analytical thresholds will provide confidence in MRD for determining a patient’s cancer status. Detecting relapse earlier will provide better outcomes for patients and help alleviate the health and economic burden of these types of disease.