After 40 years of “War on Cancer”,progress in reducing the overall cancer mortality rate has been disappointing.At the same time,many previously thought successful drugs have been withdrawn,mostly due to side-effect issues.Cancer is a disease caused by a breakdown of large parts of the cellular system (as well as higher systems) in the tumor,not just of the failure of one or two of its biological functions.Here,we used a systems approach to design optimal drug compounds for the purpose of reprogramming the tumor from an advanced state to less advanced state.We filtered out eight cancer related functional gene sets from cohort gene expression microarray data and applied the gene sets to the Connectivity Map to identify repurposed,intra-cellular side-effect free,candidate drug compounds for systems treatment of colonic adenoma.About a dozen drug compounds were identified.The top beneficial drug,GW-8510,a CDK2 inhibitor used as an adjuvant agent that protects hair-loss in chemotherapy,was highly enriched in seven cancer functional modules.Inversely,thapsigargin,known as an anticancer agent targeting endoplasmic reticulum ATPase,was identified to adversely affects several cancer functions including cancer signaling,cell proliferation,and transcription while strongly benefits apoptosis.This coincides with three previous reports that thapsigargin was a tumor promoter.Validation of these results in cell model experiments is under way.