Abstract: The emergence of mutations in tyrosine kinases following treatment of cancer patients with molecular-targeted therapy represents a major mechanism of acquired drug resistance. Here, mutations in the serpentine receptor, Smoothened (SMO) are described, which result in resistance to a Hedgehog (Hh) pathway inhibitor, such as in medulloblastoma. Amino acid substitutions in conserved residues of SMO maintain Hh signaling, but result in the inability of the Hh pathway inhibitor, GDC-0449, to suppress the pathway. In some embodiments, the disclosure provides for novel mutant SMO proteins and nucleic acids and for screening methods to detect SMO mutations and methods to screen for drugs that specifically modulate mutant SMO exhibiting drug resistance.

Abstract: Human LOC169505 genes are identified as modulators of the APC and axin pathways, and thus are therapeutic targets for disorders associated with defective APC and axin function. Methods for identifying modulators of APC and axin, comprising screening for agents that modulate the activity of LOC169505 are provided.

Abstract: Human FLJ10607 genes are identified as modulators of the Axin pathway, and thus are therapeutic targets for disorders associated with defective Axin function. Methods for identifying modulators of Axin, comprising screening for agents that modulate the activity of FLJ10607 are provided.

Abstract: Human DYRK genes are identified as modulators of the APC and Axin pathways, and thus are therapeutic targets for disorders associated with defective APC and Axin function. Methods for identifying modulators of APC and Axin, comprising screening for agents that modulate the activity of DYRK are provided.

Abstract: A post in post structure comprising a short inner post segment and a pair of hollow outer posts slipped over either end of the inner post segment and affixed to the inner post segment. The post in post structure is particularly suitable for use with a product packaging and display system of the kind having vertically spaced trays supported by outer posts 16 located over openings in each tray and inner posts inserted inside the outer support posts and through the tray openings to lock the system together.

Abstract: Human PAPSS genes are identified as modulators of the AXIN pathway, and thus are therapeutic targets for disorders associated with defective AXIN function. Methods for identifying modulators of AXIN, comprising screening for agents that modulate the activity of PAPSS are provided.