MAP2K1 and breast cancer: For instance, in MDR1-overexpressing colorectal cancer cells, degraders targeting either the kinases MEK1/2 or the oncogenic mutant GTPase KRASG12C synergized with the Lapatinib have been evaluated [46], and PI3K/AKT/mTOR inhibitors such as Copanlisib have been shown to restore lapatinib sensitivity in BC [15] and gastric cancer cell lines [54] by counteracting pathway overactivation.