PET of Signal Transduction Pathways in Cancer

In this era of systems biology, the tide of information derived from omic technologies (genomics, proteomics, etc.) has sparked a revolution in drug design, with many industrial and academic programs now embracing the concepts of molecular medicine (i.e., targeting changes in specific proteins or pathways) as measures of treatment efficacy and outcome. This approach has yielded a plethora of new preclinical therapeutics directed at novel targets within oncology. In many ways, the evolution of molecular imaging agents as diagnostic probes mirrors that of chemotherapeutics; yet despite an increasing number of PET and SPECT radiotracers being evaluated in human trials, relatively few agents have found widespread use in clinical oncology. In light of this observation, is it time to reevaluate our strategies for radiopharmaceutical design and use? In this article, we argue that PET has enormous potential to deliver clinically relevant information on disease dynamics that extends beyond mapping the density and spatial distribution of a target. Recent developments in targeting pharmacodynamic biomarkers aim to exploit better the advantages of functional PET by detecting changes in signal transduction pathways, particularly in response to disease progression or treatment in cancer.