Hence, we have further investigated the complexity of CXCL12/CXCR4/ACKR3 and EGF-RTKs signaling interplay and explored the role of GRK2 in such crosstalk in different BC cell lines corresponding either to tumors amenable to targeted therapy with low (luminal A) or high (luminal B) risk of relapse or difficult-to-treat tumours with a poor prognosis (triple-negative). The gene discussed is GRK2; the disease is breast cancer.