A bispecific antibody-drug conjugate targeting pCAD and CDH17 has antitumor activity and improved tumor-specificity.

P-cadherin (pCAD) and LI-cadherin (CDH17) are cell-surface proteins belonging to the cadherin superfamily that are both highly expressed in colorectal cancer. This co-expression profile presents a novel and attractive opportunity for a dual targeting approach using an antibody-drug conjugate (ADC). In this study, we used a unique avidity-driven screening approach to generate pCAD x CDH17 bispecific antibodies that selectively target cells expressing both antigens over cells expressing only pCAD or only CDH17.

The use of a multi-metric readout screen to identify EHMT2/G9a-inhibition as a modulator of cancer-associated fibroblast activation state.

Cancer-associated fibroblasts (CAFs) play a pivotal role in cancer progression, including mediating tumour cell invasion via their pro-invasive secretory profile and ability to remodel the extracellular matrix (ECM). Given that reduced CAF abundance in tumours correlates with improved outcomes in various cancers, we set out to identify epigenetic targets involved in CAF activation in regions of tumour-stromal mixing with the goal of reducing tumour aggressiveness. Using the GLAnCE (Gels for Live Analysis of Compartmentalized Environments) platform, we performed an image-based, phenotypic screen that enabled us to identify modulators of CAF abundance and the capacity of CAFs to induce tumour cell invasion.

An off-the-shelf multi-well scaffold-supported platform for tumour organoid-based tissues.

Complex 3D bioengineered tumour models provide the opportunity to better capture the heterogeneity of patient tumours. Patient-derived organoids are emerging as a useful tool to study tumour heterogeneity and variation in patient responses. Organoid cultures typically require a 3D microenvironment that can be manufactured easily to facilitate screening.

3D microgels to quantify tumor cell properties and therapy response dynamics.

Tumors contain heterogeneous and dynamic populations of cells that do not all display the fast-proliferating properties that traditional chemotherapies target. There is a need therefore, to develop novel treatment strategies that target diverse tumor cell properties. Identifying therapy combinations is challenging however.

Applications of Omics Technologies for Three-Dimensional Disease Models.

Omics technologies, such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, lipidomics, multiomics, and integrated modalities, have greatly contributed to our understanding of various diseases by enabling researchers to probe the molecular wiring of cellular systems in a high-throughput and precise manner. With the development of tissue-engineered three-dimensional (3D) disease models, such as organoids and spheroids, there is potential of integrating omics technologies with 3D disease models to elucidate the complex links between genotype and phenotype. These 3D disease models have been used to model cancer, infectious disease, toxicity, neurological disorders, and others.

Gels for Live Analysis of Compartmentalized Environments (GLAnCE): A tissue model to probe tumour phenotypes at tumour-stroma interfaces.

The interface between a tumour and the adjacent stroma is a site of great importance for tumour development. At this site, carcinoma cells are highly proliferative, undergo invasive phenotypic changes, and directly interact with surrounding stromal cells, such as cancer-associated fibroblasts (CAFs) which further exert pro-tumorigenic effects. Here we describe the development of GLAnCE (Gels for Live Analysis of Compartmentalized Environments), an easy-to-use hydrogel-culture platform for investigating CAF-tumour cell interaction dynamics in vitro at a tumour-stroma interface.