TOP1 and neoplasm: Considering that the PI3K/AKT pathway is constitutively active in BRCA1-defective human cancer cells [73], the combination of PTEN-related PI3K/AKT pathway inhibitors such as perifosine with DNA topoisomerase I (TOP1) or PARPi results in enhanced cancer cell killing in these tumours [74,75], suggesting a new possibly targetable pathway in case of PARPi resistance.