PREDECT is one of the major Innovative Medicines Initiatives (IMI) of the European Union with 21 laboratories collaborating in a Public-Private partnership, aiming to create more appropriate in vitro platforms for target validation and drug discovery. Genomic and proteomic data on cancers from patient material provides hypotheses regarding potential novel drug targets. Laboratory platforms to validate whether target modulation would provide a clinical benefit are usually highly reductionist, often using long-established cell lines growing in 2 dimensions in vitro. These models do not reflect the complexity of a tumour in situ, where biochemical pathways are wired with connections to the complex tumour environment provided by stromal, immune and endothelial cells. PREDECT has the goal of comparing the pathological and molecular profiles of novel in vitro platforms with those of human tumours. In a stepwise manner, material from in situ tumours will be "deconstructed," for example through tissue slices, 3-D heterogenously complex models (with stroma etc), simple 3D models, complex 2D models to simple 2D models and the profiles of each platform compared with an in situ tumour, both in the resting state and when perturbed by drugs or RNA interference. "Reconstruction" of tumor complexity will also be attempted and profiled. Proteomics of models of breast, prostate and lung cancer will be compared in a Work Package based on a centralised TMA platform, immunohistochemistry and a Web-based microscopy. A systems approach will interrogate the fidelity of in vitro platforms to represent the complexity and heterogeneity of human tumors. Because clinical material presents both logistic and quality problems for ongoing and intense studies of target validation, PREDECT aims to use material from genetically engineered mouse models, and some "advanced" xenografts, whose pathology and molecular profiles closely match cohorts of human tumours. PREDECT hopes to provide more appropriate platforms both for target validation and subsequent preclinical studies which will replace a current cascade of tests which are poorly predictive of clinical activity.

Citation Format: John A. Hickman. In vitro platforms representing tumor complexity for target validation and drug discovery. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5529. doi:10.1158/1538-7445.AM2013-5529

©2013 American Association for Cancer Research
2013