Synthetic Tuneable Peptide hydrogels for in vitro 3-dimensional Cancer Modelling and Drug Discovery

Poster
11

Synthetic Tuneable Peptide hydrogels for in vitro 3-dimensional Cancer Modelling and Drug Discovery

Authors

A Olayanju3; H Clough2; O Tsigkou2; D Lachowski1; A Del Rio Hernandez1; A Miller3
1 Imperial College London, UK;  2 University of Manchester, UK;  3 Manchester BIOGEL, UK

Abstract

Cancer is one of the most common causes of deaths worldwide. This urgent unmet clinical need is partly due to the lack of suitable efficacious therapies and the development of tumour resistance to currently
used therapies. The development of new cancer therapies involves a full mechanistic understanding of the disease’s pathogenesis, thereby allowing better targeting of cell biological pathways involved in cancer initiation and progression.

However, a major challenge in the mechanistic understanding of the disease’s pathogenesis is the lack of physiologically relevant in vitro models. Having more physiologically relevant 3D models of both healthy and cancerous tissues will allow the better understanding of
the key cellular processes and a more reliably screening of new drug entities.
Advancement in preclinical invitro 3D models, such as organoids, has made use of biomaterials to mimic the complex in vivo tumour environment; however, some widely used
biomaterials have limitations such as the lack of tuneability to fully mimic
the in vivo counterpart. Recent advances in the use of synthetic
tuneable peptide hydrogels, such as PeptiGels®, have shown potential to
overcome these limitations by better simulating tumour microenvironments for
enhanced cancer research.

Here, we demonstrate the use of PeptiGels® to generate physiologically relevant in vitro 3D breast and pancreatic cancer models to replicate healthy and diseased human tissues. PeptiGels® can be fine-tuned to recapitulate the tumour microenvironment and study
cancer-specific biology such as pH modulation, hypoxia and changes in the mechanical properties involved in cancer cell activation and survival. PeptiGel®-based
breast cancer 3D models allowed drug penetration and were resistant to Taximofen
treatment when compared to scaffold-free 2D models, potentially offering a
suitable physiologically relevant model for advanced drug discovery and
development.

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