A study published in the journal GENETICS has used mathematical models grounded in evolutionary rescue theory to propose a sharper strategy for deploying cancer drugs. Rather than waiting for tumours to regrow under treatment, the models indicate that switching therapies at the right moment can limit the rise of resistant cells and improve outcomes over standard sequential care.
The research was led by Dr Robert Noble, senior lecturer at City St George’s, University of London. His team’s paper, titled Preventing evolutionary rescue in cancer using two-strike therapy, draws on ideas long established in evolutionary biology. These same principles have proved effective against antibiotic resistance and in forecasting flu vaccine strains. Noble sees no reason they should not apply inside tumours as well.
Although tumours may at first shrink under therapy, in many cases they eventually regrow. These relapses stem from a small number of cancer cells that have gained mutations making the cells resistant to the treatment.
That observation, from Noble, captures the core problem. Standard practice often continues one drug until visible relapse, by which time resistant clones have already expanded. The new models treat each therapy as an environmental pressure. Sensitive cells die off, but any pre-existing resistant subpopulations gain room to grow. Switching while the tumour is near its minimum size, often before it is detectable again, maximises the probability that those resistant cells will die out by chance before they dominate.
The timing matters. Models show that switching after relapse has begun is generally better than switching too early. For many patients this optimal switch point would fall when the tumour is still too small to see on scans. Stochastic simulations and analytic results underpin these predictions.
Scale of the tumour shapes the number of strikes needed
A sequence of two treatments, even timed optimally, is likely to succeed only against relatively small tumours. Larger burdens demand more strikes. Noble’s team concludes that sequences of three or more therapies, each switched at the equivalent nadir, could eliminate bigger cancers.
Our models predict that this new approach will generally outperform the standard of care. A sequence of two treatments, even if optimally timed, is likely to succeed only in relatively small tumours. But we have reason to hope that switching between three or more treatments, following the same principle, could eliminate larger tumours.
Three small clinical trials inspired by this evolutionary logic are already under way, testing the concept in soft-tissue cancer, prostate cancer and breast cancer. Further trials are in development. The work prioritises measurable patient benefit through rigorous modelling and careful validation rather than untested assumptions.
