The capacity to model cancer within the mouse has advanced significantly in recent years. Perhaps the most notable technical gains have been in the development of techniques that allow the temporal and spatial control of gene expression, such that it is now possible to regulate target genes in the tissue of choice and at a given time. We have used these approaches to study tumorigenesis in the murine intestine and mammary gland. Loss of function of the tumour suppressor gene Adenomatous Polyposis Coli (Apc), has been associated with the development of both human and murine neoplasias, principally those of the intestinal epithelium. However, as Apc has been implicated in multiple cellular functions, the precise mechanisms underlying these associations remain somewhat unclear. We describe here the use of an inducible strategy to co-ordinately delete genes from the adult murine epithelium. This approach has allowed us to characterise in detail the direct consequences of inactivation of gene function. For Apc, these include failure in the differentiation programme, failure to migrate, aberrant proliferation and the aberrant induction of apoptosis. We have then been able to use this approach to directly test the efficacy of therapeutics, such as curcumin, upon these endpoints. Transcriptome analysis of this model has also identified potential new targets for therapeutic intervention, such as Sparc; deficiency of which we have now shown suppresses adenoma formation. Finally, we have been able to address how other genes modulate the consequences of Apc loss. Thus, we show that little effect following loss of CyclinD1, Tcf1 and p53; but marked differences following loss of either c-Myc or Mbd2. The models are therefore allowing us to define the earliest events associated with carcinogenesis in the intestine. Outside the intestine, we have used parallel approaches to generate murine models of mammary neoplasia, and we are now using these to accelerate the therapuetic assessment of novel agents, such as inhibitors of Parp activity.