Our findings revealed that the inhibition of anaplastic lymphoma kinase (ALK) and maternal embryonic leucine zipper kinase (MELK) selectively induces ERα degradation and prevents the proliferation of cell lines representing the LumB ERα-positive/PR-negative/HER2-positive and LumA ERα-positive/PR-positive/HER2-negative molecular phenotypes of BC, respectively. Here, PGR is linked to breast cancer.