Dataset Information

A preclinical platform for assessing long-term drug efficacy exploiting mechanically tunable scaffolds colonized by a three-dimensional tumor microenvironment

ABSTRACT: Background: Long-term drug evaluation heavily relies upon rodent models. Drug discovery methods to reduce animal models in oncology may include three-dimensional (3D) cellular systems that take into account tumor microenvironment (TME) cell types and biomechanical properties. Methods: In this study we reconstructed a 3D tumor using an elastic polymer (acrylate-endcapped urethane-based poly(ethylene glycol) (AUPPEG)) with clinical relevant stiffness. Single cell suspensions from low-grade serous ovarian cancer (LGSOC) patient-derived early passage cultures of cancer cells and cancer-associated fibroblasts (CAF) embedded in a collagen gel were introduced to the AUPPEG scaffold. After self-organization in to a 3D tumor, this model was evaluated by a long-term (>40 days) exposure to a drug combination of MEK and HSP90 inhibitors. The drug-response results from this long-term in vitro model are compared with drug responses in an orthotopic LGSOC xenograft mouse model. Results: The in vitro 3D scaffold LGSOC model mimics the growth ratio and spatial organization of the LGSOC. The AUPPEG scaffold approach allows to test new targeted treatments and monitor long-term drug responses. The results correlate with those of the orthotopic LGSOC xenograft mouse model. Conclusions: The mechanically-tunable scaffolds colonized by a three-dimensional LGSOC allow long-term drug evaluation and can be considered as a valid alternative to reduce, replace and refine animal models in drug discovery

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Jarne Pauwels

LAB HEAD: Olivier De Wever

PROVIDER: PXD039590 | Pride | 2024-01-26

REPOSITORIES: Pride

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			Action	DRS
	F000819_1p_uPAC8_PRC-4907_DeWeverLab_TMT10plex_fraction-1.raw	Raw
	F000821_1p_uPAC8_PRC-4907_DeWeverLab_TMT10plex_fraction-2.raw	Raw
	F000823_1p_uPAC8_PRC-4907_DeWeverLab_TMT10plex_fraction-3.raw	Raw
	F000825_1p_uPAC8_PRC-4907_DeWeverLab_TMT10plex_fraction-4.raw	Raw
	F000827_1p_uPAC8_PRC-4907_DeWeverLab_TMT10plex_fraction-5.raw	Raw

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A preclinical platform for assessing long-term drug efficacy exploiting mechanically tunable scaffolds colonized by a three-dimensional tumor microenvironment.

De Vlieghere Elly E Van de Vijver Koen K Blondeel Eva E Carpentier Nathan N Ghobeira Rouba R Pauwels Jarne J Riemann Sebastian S Minsart Manon M Fieuws Charlotte C Mestach Johanna J Baeyens Ans A De Geyter Nathalie N Debbaut Charlotte C Denys Hannelore H Descamps Benedicte B Claes Kathleen K Vral Anne A Van Dorpe Jo J Gevaert Kris K De Geest Bruno G BG Ceelen Wim W Van Vlierberghe Sandra S De Wever Olivier O

Biomaterials research 20231018 1

<h4>Background</h4>Long-term drug evaluation heavily relies upon rodent models. Drug discovery methods to reduce animal models in oncology may include three-dimensional (3D) cellular systems that take into account tumor microenvironment (TME) cell types and biomechanical properties.<h4>Methods</h4>In this study we reconstructed a 3D tumor using an elastic polymer (acrylate-endcapped urethane-based poly(ethylene glycol) (AUPPEG)) with clinical relevant stiffness. Single cell suspensions from low- ...[more]

PMID: 37853495

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