Drive outcomes in oncology
Dysregulated metabolism is not only essential for the growth and proliferation of individual cancer cells; indeed, the physiology of the patient is as much a part of the equation as the tumor. Metabolomics can both identify cancer-specific drug targets and assess the patient’s phenotype more broadly, addressing key questions like who will respond to the therapy? How can we expand the pool of responders? How can we predict adverse events? Overall, metabolomics informs decision-making and positions development programs for success by providing a functional readout of the molecular phenotype.
Drug development in oncology often suffers from “Achilles heel” traits such as an absence of human genetic data linking the target to the disease, lack of access to a well-validated animal model of the disease or poor understanding of the target’s role in the underlying disease pathophysiology. Metabolomics has the capacity to arm your program for success by illuminating the right target through profound mechanistic understanding of the disease state.
It’s not always easy to predict toxicity from preclinical data or to demonstrate clear drug exposure and pharmacological activity on the target organ, but metabolomics can help ensure the right exposure and right safety profile by providing early biomarkers of both on- and off-target activity and toxicity.
A lack of efficacy biomarkers and an inability to stratify patients are among the leading causes of project failure. Metabolomics delivers the transformational key to identify the right patients & biomarkers as well as the right commercial potential.
The critical influence of the gut microbiome on the efficacy of immuno-oncology drugs is now well-established. How do microbes in the gut drive patient response in distal organs? Metabolomics provides a key piece of the puzzle by profiling the chemical signals that mediate the microbial modulation of host immunity. What’s more, the importance of metabolic reprogramming in T cell activation makes metabolomics a crucial tool in the development of robust and reproducible manufacturing processes for CAR-T and other cell-based therapies.
Reference: Based on AstraZeneca’s five-dimensional framework Cook, D, et al. Nat Rev Drug Discov 13, 419–431 (2014).