Looking Backward and Forward at Cancer-Associated Mutations With Precision Genome-Editiing - Sam Gould

This PhD thesis defence uses high-throughput CRISPR variant engineering to study how cancer mutations drive tumour behaviour. A prime-editing sensor enables efficient functional screening of ~1,000 TP53 patient variants, revealing effects missed by cDNA overexpression. Directed base-editing screens map resistance mutations across CDKs and drug modalities, predicting clinically relevant therapy response.