E2F4 and neoplasm: In the presence of chemotherapy with irinotecan, on the other hand, CRCs engineered to express the E2F4-shRNA construct displayed a substantial increase in drug sensitivity, as revealed by the systematic observation of profound reductions in average tumor volumes and growth rates, superior in magnitude to those observed in control tumors (i.e., statistically significant in 2-way and 3-way ANOVA tests for interaction between E2F4 knock-down and chemotherapy) and often associated with prolonged tumor shrinkage (which is usually not observed when using irinotecan alone).