Mimicking and analyzing the tumor microenvironment

Cell Reports Methods, Journal Year: 2024, Volume and Issue: 4(10), P. 100866 - 100866

Published: Sept. 30, 2024

The tumor microenvironment (TME) is increasingly appreciated to play a decisive role in cancer development and response therapy all solid tumors. Hypoxia, acidosis, high interstitial pressure, nutrient-poor conditions, cellular heterogeneity of the TME arise from interactions between cells their environment. These properties, turn, key roles aggressiveness resistance disease, through complex reciprocal cell genotype phenotype, physicochemical Understanding this complexity requires combination sophisticated models high-resolution analysis tools. Models must allow both control acellular analyses be able capture at depth spatial resolution. Here, we review advantages limitations methods order guide further research outline future challenges.

Language: Английский

Innovating cancer drug discovery with refined phenotypic screens

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(8), P. 723 - 738

Published: July 15, 2024

Before molecular pathways in cancer were known to a depth that could predict targets, drug development relied on phenotypic screening, where the effectiveness of candidate chemicals is judged from functional readouts without considering mechanisms action. The unraveling tumor-specific has brought targets for molecularly driven discovery, but precedents field have shown awareness does not necessarily therapeutic efficacy, and many cancers still lack druggable targets. Phenotypic screening therefore retains niche targeted approach informative. We analyze unique advantages screens, how technological advances improved their discovery power. Notable include use larger biological panels refined protocols address disease-relevance increase data content with imaging omic approaches.

Language: Английский

Leveraging Crosslinker Diffusion to Template Stiffness Gradients in Alginate Hydrogels

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 29, 2024

Abstract Mechanobiology or the response of cells to forces mechanical properties their environment drives many physiological and pathological processes including development, wound healing, fibrosis cancer. A variety cell biological behaviors are driven by local stem differentiation drug resistance. Furthermore, can sense stiffness gradients migrate up gradient in a process called durotaxis. The development 3D hydrogel systems with tunable patterns affords ability run multiple experiments at different stiffness. This is critical as some behavior not monotonically dependent upon Additionally, creation property within hydrogels may be able guide particular targets forming complex cellular structures enhancing healing through directed migration. In this paper, we developed an approach spatially imprint alginate hydrogels, that used probe mechanobiology. Stencils were easily designed fabricated using common craft cutter control presentation calcium crosslinking solution gels. Different stencil shapes result opacity imprinted into both thick thin gels arbitrary shape. steepness well maximum controlled based on reproducible kinetics regulated concentration developing time. Calcium results changes increases elastic modulus bulk hydrogel. Opacity correlates modulus, allowing it proxy for modulus. Consequently, spatial also stenciling approach. represents facile way Graphical

Language: Английский