Wim Vanden Berghe
Cell Death Signaling Lab-IPPON, Department Biomedical Sciences, UAntwerp

Disease relapse and therapy resistance remain key challenges in cancer treatment. Underlying (epi-)mutational events typically promote tumorigenesis and contribute to multi-drug therapy resistance.  Although innovative biomarker “omic” strategies (genome-epigenome-transcriptome-proteome-metabolome-lipidome) are instrumental to optimize personalized precision oncology treatments, diagnostic signatures remain challenging due to (epi)genetic plasticity of (immunogenic) cell death signaling pathways and tumor-immune microenvironment heterogeneity, causing therapy escape, which prevents complete recovery and ultimately triggers disease relapse. Tailoring oncology treatments by multiplex, functional kinase activity profiling technology holds immense potential in overcoming the current challenges posed by cancer-tumor microenvironment heterogeneity to improve patient outcomes. Kinases are the most intensively studied protein targets and are the basis of numerous types of cancer therapies. However, the traditional -omic approaches study the abundance of proteins rather than their activity. This results in a knowledge gap on how cell signaling really works and a partial understanding of cancer drug mechanism of action (i.e. specificity, efficacy).  Phoshopeptidome based kinome activity phenotyping reveals the bigger picture of cellular signaling and provides mechanistic biological insights needed to fully understand cellular signaling bypasses upon therapy resistance.