Patent ID: 8394742

Claim:
A method for identifying molecules that reduce viability of cancer cells with a specific pattern of a loss-of-function genetic alteration comprising the steps of: (a) creating a matched pair of isogenic cell lines that differ only by a “knock down” of expression of a single DPC4 gene wherein the “knock down” of expression of the single DPC4 gene is achieved by RNA interference performed by transfection or transformation of the cell line with a vector including therein in sequence: (1) DNA encoding a sequence selected from the group consisting of: 5′-ATGTCTATTACGAATACAC-3′ (SEQ ID NO: 1); 5′-TGCCCGTCTCTGGAGGTGG-3′ (SEQ ID NO: 2); 5′-ATCGTGCATCGACAGAGAC- 3 ′ (SEQ ID NO: 3); 5′-GTAGGACTGCACCATACAC-3′ (SEQ ID NO: 4); 5′-GGTCAACTCTCCAATGTCC-3′ (SEQ ID NO: 5); and 5′-AGCAAGGTTGCACATAGGC-3′ (SEQ ID NO: 6); (2) DNA encoding a spacer sequence; and (3) DNA encoding the reverse complement of the selected sequence; (b) screening a molecular library against the matched pair of isogenic cell lines to identify a molecule that exerts a differential effect on cell survival such that cell survival is diminished to a greater extent in the cell line that exhibits “knock down” of expression of the single DPC4 gene; and (c) confirming the differential effect in a tumor model selected from the group consisting of an in vivo tumor model and an in vitro tumor model to identify the molecules.