Using this approach, we were able to down regulate the activity of GLI proteins as well as the up regulation of the output onco-proteins (See the treatment scenarios of Figures 4, 5 and 6) by perturbing the over expressions of few optimal combinations of proteins (SMO, GLI1, GLI2 in Glioma Grade IV cell line; SMO, HFU, ULK3 and RAS in Colon cancer cell line; and SMO, HFU, ULK3, RAS and ERK12 in pancreatic cancer cell line). This evidence concerns the gene GLI2 and malignant colon neoplasm.