Professor Caroline Dive CBE
Director CRUK Manchester Institute Cancer Biomarker Centre, University of Manchester, UK and President of the The European Association for Cancer Research
Whilst a lot of progress has been made in personalised cancer medicines, there is still a lot to learn in order to take the next step in the war on cancer. Could early detection be the key?
A wealth of data tells us that detecting cancer earlier brings patient benefit. If we know this is critical, then why have breakthroughs been sparse? Part of the answer is because it is so challenging to achieve.
Where are the knowledge gaps?
Basic research on the biology of early cancers has not yet received sufficient attention. Early detection research requires large clinical studies, multidisciplinary teams and a substantial amount of funding. Better preclinical models of early cancers are needed to understand the early events at the molecular level that occur within a developing tumour and its impact on surrounding normal tissues.
The earliest changes in the immune system as a tumour begins to develop are incompletely understood. Picking up tumour specific changes with a non invasive approach in asymptomatic individuals seems a very tall order.
Moreover, if non-invasive biomarkers are developed that do not pinpoint the location of tumour, at a timepoint when resolution of imaging approaches to guide surgery is not possible, how will these individuals be managed? The challenge of over diagnosis looms large as early biomarker tests emerge and these tests will need to distinguish indolent (leave them alone) from aggressive (intervene early) lesions.
The progress being made with circulating tumour DNA (ctDNA) in the bloodstream is truly exciting, where a methylation profile acts as a tumour zip code.
Liquid biopsies for early cancer detection
The liquid biopsy field (the diagnosis or analysis of tumours using only a blood or fluid sample) has exploded in the past decade. Circulating proteins (e.g. prostate specific antigen) are established in clinical use and circulating nucleic acids are routinely used testing for prenatal testing.
Liquid biopsies are entering cancer clinics to predict treatment benefit, but their impact to identify molecular profile consistent with early and aggressive tumour formation has yet to be delivered as a screening test.
However, the progress being made with circulating tumour DNA (ctDNA) in the bloodstream is truly exciting, where a methylation profile acts as a tumour zip code. The final push may be a multimodal approach, where methylated ctDNA and ctDNA fragment size add power to mutation detection, with circulating tumour cell analysis that yields the tumour genotype (genetic constitution) and phenotype (observable characteristics) of aggressive early invaders.
Who do we screen?
Should we ‘fish’ in a well stocked lake (a high cancer risk cohort) or in the ocean (whole population) to develop our early detection liquid biopsies? Both approaches are underway, with cancer specific (e.g. high risk for lung cancer) and pan cancer studies ongoing.
Finally, could we see more early detection in the future? It’s Tuesday, your device buzzes, a reminder to put your bi-monthly blood sample in at your community pharmacy for cancer screening. Well, I wouldn’t bet against this vision becoming reality.
