30 March 2020
Cancer researchers based in India are invited to submit proposals for funding to support the integration of biological pathways related to cancer, building on the concept from the field of toxicology of Adverse Outcome Pathways (AOPs). More information on how to apply »
The need for this type of human-relevant research is evident. Cancer claims millions of lives worldwide each year. Yet, despite relentless efforts to find a cure, 97 percent of cancer drugs that reach clinical trials never make it to market. This points to a failure of our drug discovery pipeline, which relies heavily on animal testing. Back in 1997, Dr Richard Klausner, director of the U.S. National Cancer Institute, famously said, “The history of cancer research has been a history of curing cancer in the mouse. We have cured mice of cancer for decades – and it simply didn’t work in humans.” Sadly, little has changed since then. Further pursuit of cancer research in rodents — even ‘humanized’ rodents containing one or two human genes — will not get us where we need to go in our quest for a cure. Luckily, technological advances and a deeper understanding of human biology are on our side. The ability to treat cancer has improved in recent years because of growing insights into human biology, including gene expression studies that give us a window into inter-tumour and inter-individual variability. Tissue heterogeneity, with respect to the variety of abnormal cell types, as well as the different abilities of proliferation, migration, and response to therapy make cancer a difficult disease to tackle.
A deep understanding of disease biology, and specifically human biology, is critical to advancing human cures. There is much we still don’t know about cancer biology, and most of what we do know is divided among different databases, journals or papers, or within the minds of experts. To bring all this information together in a structured manner, the Organization of Economic Cooperation and Development (OECD) has adopted an organizing framework called “Adverse Outcome Pathways” or “AOPs”. AOPs link initial events at the molecular level through all levels of biological organization to the manifestation of an “adverse outcome” in the form of toxicity or disease.
Originally designed for relating molecular changes to pathological outcomes following chemical exposure, AOPs are equally useful to understand diseases like cancer, whether or not the cause is chemical exposure. The OECD AOP Development Program is a multinational crowdsourcing effort to collect, organize and evaluate biological information into a wiki-based knowledge management tool. Such a tool could provide a more predictive and effective rubric for understanding disease pathophysiology across levels of biological organization. It can also be used to target and evaluate new interventions using the growing toolbox of modern, human-specific approaches, such as 3D tissue models, microfluidic organs-on-a-chip, and computational systems biology modelling.