Application of epigenetic therapies in combination with cyclin dependent kinase inhibitors (CDKIs) in patients with metastatic breast cancer to reverse tumor resistance: two case reports

CDKIs are widely used to treat breast cancer and recently suggested in treating manyother types of cancer, such as ovarian cancer, pancreatic cancer, and gliomas. Unfortunately however, resistance to such drugs develops in almost all cases after a few months to a year; thisgives the tumor selective advantage by allowing it access to other passenger promoter genes. Several mechanisms of resistance have been explored in the literature ranging from Rb1 mutations to epigenetic aberrancies as a result of using this class of drugs. Here we go over two cases of advanced stage four breast cancer treated with Palbociclib with initial response but eventual resistance. Patients were then started on epigenetic therapies to reverse resistance whichwas met with improved treatment response as evident by clinical and radiological measures. We conclude that the addition of multitargeted epigenetic therapies (MTET) to this class of drugs is clinically impactful by preventing/reversing tumor resistance and further providing possible synergistic effects of biological modifiers.