Exploiting molecular genomics in precision radiation oncology: a marriage of biological and physical precision

Achieving local tumour control is paramount for cure in head and neck and prostate cancers. With the transition to precision radiotherapy (RT) techniques, survival rates have improved in the majority of these cancers, but a substantial proportion of 30–40% still relapse following primary treatment. Recent large-scale molecular profiling studies have revealed unique biological events that could explain for tumour aggression and resistance to therapies, redefining the molecular taxonomy of head and neck and prostate cancers. Here, we reviewed the key findings from these studies, highlighting those relevant for clinical stratification. We also proposed novel combinatorial clinicomolecular models to identify subsets of patients with aggressive localised tumours and limited metastases, and to inform on the optimal management of these patients using molecular targeted agents, immunotherapy, and RT.