 Cells containing oncogenic mutations in-vivo often responded by activating the INK4A/ARF/INK4B locus that encodes the INK4 tumor suppressor proteins.The unusual genomic arrangement of the INK4a/ARF/INK4b locus functions as a weakness in our anti-cancer defenses.This is due to the fact that three crucial regulators of the RB and p53 (regulated by ARF) are vulnerable to one single, small deletion.