In the present work, we focused on PI3Ka-mutated breast cancer models and we explored the efficacy of blocking AKT signaling trough direct inhibition of PI3Ka with taselisib or downstream inhibition of AKT protein with ipatasertib and their combination with the most widely used chemoterapeutic agents for MBC, the class of anti-microtubules (vinorelbine, eribulin, paclitaxel). The gene discussed is AKT1; the disease is breast cancer.