Orion is participating in PREDECT, a joint initiative between academic laboratories, biotechs and the pharmaceutical industry. One of the project’s goals is that it should eventually improve the clinical success of therapies designed for the treatment of cancer. The network develops innovative models and technologies for the preclinical evaluation of cancer therapy targets.

There has been an explosion, in the last decade, of the knowledge regarding the genetic changes that are associated with cancer. This knowledge provides great opportunities for improved, selective treatments through the design of new drugs and antibodies that are targeted specifically to those changes in tumour cells responsible for the survival, proliferation and spread of the cancer. A challenge for drug discovery is to establish which of the many molecular changes associated with a particular cancer type, in a particular patient subgroup, are responsible for the pathology and which are associated “bystanders” playing a minimal or no role.

Accumulating information suggests that an alarmingly high proportion of new drugs, targeted to recently-identified molecular changes in cancer, lack efficacy when tried in patients. One reason for this lack of efficacy may reflect the use of over-simplified laboratory models of cancer that do not represent the complexity and heterogeneity of tumours. In these “reductionist” models promising drug targets may not work as they would in a cancer patient and consequently drug inhibition has only a modest or no effect clinically.

Advanced research methods

PREDECT sets out to provide new laboratory models of human cancer that better reflect the complexity and heterogeneity of cancers. Working in teams investigating breast, prostate and lung cancers, PREDECT will use advanced mouse models of cancer, some of which will be genetically engineered and matched to particular groups of patients with these cancers, to progressively “deconstruct” the complex tumours into simpler forms for use on the laboratory bench.

Examples are thin slices of tumour tissue and tumour cells growing in three-dimensions together with supporting cells, rather than the simple, conventional two-dimensional models. At each stage of the reduction of complexity, the tumour cells will be profiled to establish how closely they represent the tumour of origin, growing in vivo, and thus how closely they represent a human tumour. Novel complex models with the appropriate profiles can eventually be used to validate that a new, potential target for cancer treatment is worth pursuing.

The PREDECT project will provide robust technologies permitting the biotechnology and pharmaceutical industry to take early decisions on whether or not to invest in and pursue an intensive drug discovery programme on a new target, reducing wasted effort. If the technologies suggest the target is valid, these PREDECT platforms will also permit early validation of biomarkers indicating which cohorts of patients would be suggested to benefit from the drug, increasing the likelihood of success for the patient in clinical trial, and decreasing trial duration and expense. Additionally, laboratory models that better represent cancer pathologies will permit academic researchers to perform investigations of tumour biology with greater fidelity.

Professor John Hickman, Coordinator for Servier of the PREDECT consortium comments:

“The Innovative Medicines Initiative has allowed cancer researchers in Industry to come together to determine which are the bottlenecks in the drug discovery process that limit the emergence of more effective cancer therapies. We believe that inadequate laboratory models to investigate and validate potential targets have contributed to the failure of recent clinical trials where the drugs lacked efficacy. To create innovative technologies and platforms, more representative of the complexities associated with human tumours, we need top-flight academic expertise in cancer cell biology, bioinformatics and systems biology to complement our efforts in drug discovery.”

Dr Emmy Verschuren, academic coordinator and representative of the IMI funding Managing Entity at the Institute for Molecular Medicine Finland, University of Helsinki, weighs in:

“PREDECT is very timely. It is absolutely essential to comprehensively re-factor our model systems now, but it is also a significant task that requires academia and industry to pull together.”

Pharmaceutical companies involved in PREDECT are Hoffmann-La Roche, Bayer Schering Pharma, AstraZeneca, Boehringer Ingelheim International, Orion Pharma, Sigma-Tau and Servier whose total in-kind contributions to the project are matched by funding from the IMI Joint Undertaking, resulting in a total of 17.2 Million Euros.

The academic and biotechnology company expertise essential to the programme is provided by The University of Helsinki, Biomedicum Genomics Ltd and VTT Turku (Finland), University of Tartu (Estonia) Radboud University Nijmegen and Erasmus University Rotterdam (Netherlands), Institute of Cancer Research (UK), Oncotest GMbH and the Margarete Fischer-Bosch Institute (Germany), Ecole Polytechnique Fédérale Lausanne (Switzerland), Weizmann Institute (Israel) and Instituto de Biologia Experimental e Tecnológica (Portugal).

The five year PREDECT program is funded by Innovative Medicines Initiative (IMI).

Read more about the project at www.predect.eu.