Fig. 3.

Resistance and therapy. A Even fully clonal tumours can develop resistant subclones during therapy. New mutations can be caused by external factors, such as radiation, or by internal reprogramming, such as upregulation of error-prone DNA polymerase and downregulation of DNA repair mechanisms. B Tumours with minor resistant subclones are likely to re-emerge after therapy. To avoid this, tumours should undergo detailed characterisation, for example by multisampling or using single-cell analysis. C In tumours harbouring multiple subclones, treatments—such as vaccines—should target truncal (i.e. present in every tumour cell) targets