Mutations in the tumour suppressor p53 are a major barrier to cancer therapy across diverse cancer types. Accordingly, patients with p53 mutated cancers often have a worse prognosis and poor outcomes. BH3-mimetic drugs were postulated to be a game changer for mutant p53 cancers because they act downstream in the apoptotic pathway to inhibit BCL-2 pro-survival proteins to induce death. However, even these anti-cancer drugs have now been shown to rely on p53 function for maximal activity. In order to improve therapy for people with mutant p53 cancers we need a better understanding of the role of mutant p53 in cancer development, sustained growth and therapy responses. To address this, we generated two sophisticated mouse models in which we can move between different p53 states (mutant, wild-type and knockout) at will. We have crossed these 'switchable p53 mice' with mouse models of MYC-driven lymphoma and mutant KRAS driven lung cancer to better understand how best to treat these cancers. Our data suggests that mutant p53 does not have gain-of-function effects that are required for tumour growth. Therefore, drugs that degrade or inactivate mutant p53 would not have therapeutic benefit. Rather, drugs that could restore wild-type p53 functions would have more therapeutic impact.