Lay summary
This programme focusses on understanding how the TP53 gene network, especially p53 isoforms, contributes to cancer, and using this information to develop clinically useful information and tools. We will: (i) verify that high levels ∆133T53b isoform predict which patients will develop aggressive disease and develop a clinically useful biomarker (ii) learn more about the cancers with high levels ∆133T53b by characterising the immune cell infiltration; (iii) use CRISPR to identify mechanisms of isoform function; (iv) develop novel strategies to target cancers with elevated levels of ∆133p53 isoforms, including immunotherapy and (v) develop more refined future biomarkers using advanced statistical tools to compare each tumour’s immune status and clinical features of cancer patients. With these broad approaches we will develop an in depth understanding of how the TP53 network contributes to cancer which will provide clinically translatable information leading to new prognostic markers and new therapies.