Importantly, the combination of PIN1 inhibitors with CDK4 inhibitors creates a positive feedback loop of PIN1 inhibition and APC/CCDH1 activation to irreversibly degrade PIN1 and other crucial mitotic proteins, resulting in permanent cell cycle exit and an anti-cancer immune response, which translates into synergistic efficacy against TNBC, including those RB-deficient tumors. Here, APC is linked to cancer.