The adverse outcome pathway for breast cancer: a knowledge management framework bridging biomedicine and toxicology

Abstract

Breast cancer is the most common cancer worldwide, with an estimated 2.3 million new cases diagnosed every year. Effective measures for cancer prevention and cancer therapy require a detailed understanding of the individual key disease mechanisms involved and their interactions at the molecular, cellular, tissue, organ, and organism level. In that regard, the rapid progress of biomedical and toxicological research in recent years now allows the pursuit of new approaches based on non-animal methods that provide greater mechanistic insight than traditional animal models and therefore facilitate the development of Adverse Outcome Pathways (AOPs) for human diseases. We performed a systematic review of the current state of published knowledge with regard to breast cancer to identify relevant key mechanisms for inclusion into breast cancer AOPs, i.e. decreased cell stiffness and decreased cell adhesion, and to concurrently map non-animal methods addressing these key events. We conclude that the broader sharing of expertise and methods between biomedical research and toxicology enabled by the AOP knowledge management framework can help to coordinate global research efforts and accelerate the transition to advanced non-animal methods, which, when combined into powerful method batteries, closely mimic human physiology and disease states without the need for animal testing.

Unleashing the potential of cell painting assays for compound activities and hazards prediction

“…Arguably, morphological fingerprints may readily assess what MoA a compound may be acting through in human cells. Such information could, for example, inform the development of anti-tumour compounds ( von Coburg and Dunst, 2023 ) or be used in the assessment of human health or environmental risk of industrial chemicals ( Nyffeler et al, 2023 ). Thus, the introduction of CP opens the route for a paradigm shift towards a more comprehensive assessment of compound effects.…”