However, another study explored the resistance mechanisms of TKIs, including tucatinib, through gene profiling of different HER2- and non-HER2-overexpressing breast cancer cell lines [75], and identified three novel markers relevant to TKI sensitivities: V-set domain-containing T-cell activation inhibitor 1 (VTCN1), cyclin-dependent kinase 12 (CDK12), and Ras-related C3 botulinum toxin substrate 1 (RAC1). This evidence concerns the gene CDK12 and breast cancer.