MDM2 and cancer: As a consequence of insufficient apoptosis induction by MDM2 antagonists, cancer cells are given the time to gain additional mutations and eventually develop drug resistance, as reported initially for the first generation MDM2 antagonist, Nutlin-3a [18,19,20], and later for additional compounds, i.e., SAR405838 [21,22], MI-63 [23], and HDM201 [24].