They showed that SPOP, the most commonly mutated gene in both clinically localized and metastatic PCa, modulates DNA DSB repair and that organoids with SPOP mutation show increased levels of genomic instability.68 Alterations in SPOP cause impaired HRR similar to tumors with BRCA1 mutations.68 Further experiments presented evidence that SPOP mutations sensitize to PARPi,68 but no clinical trials have been conducted to explore the relevance of these preclinical findings. The gene discussed is BRCA1; the disease is posterior cortical atrophy.