Analogously, PDK1 was affirmed to be a key modifier of acquired resistance to CDK4/6 inhibitors in ER-positive BC cells via the PI3 K/PDK1 pathway in both AKT-dependent and AKT-independent manners, and the combination of CDK4/6 inhibitor ribociclib or palbociclib and PDK1 inhibitor GSK2334470 synergistically suppressed proliferation and increased apoptosis in several ER+ BC cell lines in vitro and in vivo [80]. The gene discussed is CDK4; the disease is breast cancer.