Tailored Colorectal Cancer Drug Combinations Proposed with Modeling, Organoid Approach

In Journal of Experimental and Clinical Cancer Research, researchers from the University of Geneva and elsewhere present a personalized cancer treatment strategy that relies on ex vivo organoid testing and mathematical modeling to focus in on optimized drug combinations — an approach they applied to primary and metastatic colorectal cancer (CRC) cases. Starting with a "Therapeutically Guided Multidrug Optimization" (TGMO) phenotypic method, the team tracked down a handful of optimized drug combinations (ODCs) with apparent activity in three-dimensional CRC models, subsequently testing the ODCs in patient-derived organoids from primary or metastatic CRC cases that were further assessed by exome and RNA sequencing. "Optimizing low-dose synergistic drug combinations is an attractive strategy to tackle the complex machinery of cancer and to overcome, or more importantly, to prevent acquired drug resistance," they write. "The simultaneous targeting of key signaling pathways at different levels or targeting distinct signaling pathways is essential to efficiently kill cancer cells.