What question did this study set out to answer?

This investigation aims to understand how the tumour microenvironment affects cancer cell behavior and drug responses through mechanistic insights.

April 5, 2026

Abstract 769: Matrix mechanics modulate cancer cell plasticity and drug responses.

Puntos clave

This investigation aims to understand how the tumour microenvironment affects cancer cell behavior and drug responses through mechanistic insights.
Developed in vitro models using 2D hydrogel micropatterning and 3D bioprinted matrices.
Created spatially controlled environments reflecting the biochemical and biophysical cues of in vivo tumours.
Analyzed cancer cell responses to varying stiffness and confinement in engineered substrates.
Changes in matrix stiffness and confinement significantly reorganized cancer cell populations.
Softer 3D matrices increased the prevalence of stem-like cancer cells with higher invasiveness and drug resistance.
The study emphasizes the importance of matrix mechanics in cancer evolution and therapy response.

Resumen

Abstract The ability of cancer to adapt and evolve within its microenvironment drives metastasis and therapy resistance, with cancer cell plasticity playing a central role in these processes. To uncover how the tumour microenvironment (TME) shapes cancer cell behaviour to influence drug responses, we built next-generation in vitro models that recapitulate the key biophysical and biochemical cues of in vivo tumours. Using precision-engineered 2D hydrogel micropatterning techniques and 3D bioprinted matrices, generated with the RASTRUM™ platform, we created spatially controlled “tumour environments" where cancer cells experienced defined stiffness, confinement, and extracellular matrix (ECM) architecture and composition. These mechanically tunable systems enabled interrogation of how substrate-cancer cell interactions and matrix mechanics orchestrate cellular transitions, organisation, and standard-of-care drug responses across cancer models. Our results reveal that subtle changes in stiffness and confinement dramatically reorganise cancer cell populations, mimicking spatial hierarchies observed in vivo. In 3D, softer matrices enriched stem-like cancer subpopulations with increased invasiveness potential and chemoresistance, underscoring the powerful influence of matrix mechanics on tumour evolution. Together, these bioengineered platforms offer an accessible, high-throughput approach for investigating the mechanical underpinnings of cancer cell plasticity. By merging bioprinting precision with biological complexity, this work lays the foundation for more predictive models of tumour progression and opens new avenues for developing approaches targeting resistant cancer cell states. Citation Format: Chantal Kopecky, Elvis Pandzic, Morgan Hamon, Sean Porazinski, Justin Gooding, Kristopher A. Kilian. Matrix mechanics modulate cancer cell plasticity and drug responses abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 769.

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Cite This Study

Kopecky et al. (Fri,) studied this question.

synapsesocial.com/papers/69d1fd3da79560c99a0a3280 https://doi.org/https://doi.org/10.1158/1538-7445.am2026-769

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