Abstract

Every cancer patient poses a distinctive challenge to physicians. Colorectal cancer is not one but rather a collection of similar diseases of abnormal tissue growth in the colon. Due to the variable underlying disease biology - for instance in genetic make-up, metabolism or environmental factors - tumours targeted by a drug may respond well to treatment in one but not in another person. Current strategies to match the right drug to a patient’s tumor, in other words precision medicine, often rely on genomic criteria. However, genomic screens do usually not provide the actionable and functional information required by a precision medicine strategy. Morphological profiling enables collecting detailed information on the shape and the size of single cells and their compartments. Here, we want to assess whether and how morphological profiling can supplement current precision medicine strategies. 

To capture an abundance of information about the single-cell responses, we adopt a promising technique from the field of phenotypic drug screening. Cell Painting can - by using an optimized mixture of dyes - characterize cells down to the organelle level. To reflect tumor heterogeneity, we use distinct cell lines from the COREAD, a panel of colorectal cancer cell lines whose heterogenous proteomic landscape is well-characterized.​ Finally, we subject the cells to a library of clinically relevant compounds with broad mechanisms of actions. By capturing a vast amount of cellular information of diverse cells in distinct conditions, we aim to map the morphological space of cells within a colorectal cancer context. Ultimately, we believe that such an approach allows us to identify interesting compounds that potentially reveal disease heterogeneity and drug response mechanistic insight.