These data collectively indicate that Erbb2 along with the Notch signaling axis plays a key role in 75% of wt KRAS CRC (with respect to codons 12/13, 61 and 146) tumors and systematic delineation of tumor dependence on these pathways using a functional CANscript platform could aid crafting of combinatorial strategies for effective therapeutic interventions. The gene discussed is ERBB2; the disease is colorectal carcinoma.