PREDECT is an IMI-funded partnership between 9 academic, 3 SME and 9 EU pharmaceutical company partners, developing advanced, transferable in vitro models for breast, prostate and lung cancers.
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. Partners include pharmaceutical industry, academic and biotech laboratories. 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 and heterogeneity of a tumour in situ, where biochemical pathways are wired with connections to the complex tumour environment provided by the stroma.
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, 3D 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 obtention of clinical material presents both logistics 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 in vitro platforms both for target validation and subsequent preclinical studies which will replace a current cascade of tests which are poorly predictive of clinical activity.The project is expected to shift paradigms in cell biology as well as in preclinical target validation where it should permit greater predictivity of drug efficacy in patient cohorts.
More information on the IMI initiative can be found on their webpages: http://www.imi.europa.eu/.