While we hypothesize that G1 to S transition and Rb inactivation are in part required for histone deacetylase inhibitor-induced apoptosis in neoplastic colonic cells, we also posit that aberrant cell cycle in p300-deficient colorectal cancer cells, including premature Rb inactivation and accelerated entry into S phase, inhibits the energy stress required for apoptosis. The gene discussed is RB1; the disease is colorectal cancer.