Patient-derived ovarian cancer explants: preserved viability and histopathologic

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Patient-derived ovarian cancer explants: preserved viability and histopathologic

Friday, 05.02.2021

Ovarian carcinoma remains a major therapeutic challenge due to its tendency to develop resistance after initial response to chemotherapy. In this work, a collaboration between iBET, AbbVie and IPOLFG, we developed ovarian carcinoma patient-derived explant (OvC-PDE) cultures that retained architecture and cell type heterogeneity of the original tumour. This patient-derived model have potential applications in the study of drug response and resistance mechanisms and in the development of innovative precision medicine approaches.


Sofa Abreu1,2, Fernanda Silva3, Rita Mendes1,2, Teresa F. Mendes1,2, MartaTeixeira1,2, Vítor E. Santo1,2, Erwin R. Boghaert4, Ana Félix 3,5 & Catarina Brito 1,2

1 iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780‑901 Oeiras, Portugal.

2 Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Avenida da República, 2780‑157 Oeiras, Portugal.

3 Centro de Estudos de Doenças Crónicas da Faculdade de Ciências Médicas, CEDOC-FCM-NOVA, Universidade Nova de Lisboa, R. Câmara Pestana 6, 1150‑078 Lisbon, Portugal.

4 AbbVie, 1 North Waukegan Road, North Chicago, IL 60064‑6098, USA.

5 IPOLFG, Instituto Português de Oncologia de Lisboa Francisco Gentil, R. Prof. Lima Basto, 1099‑023 Lisbon, Portugal.


Ovarian carcinoma (OvC) remains a major therapeutic challenge due to its propensity to develop resistance after an initial response to chemotherapy. Interactions of tumour cells with the surrounding microenvironment play a role in tumour survival, invasion capacity and drug resistance. Cancer models that retain tissue architecture and tumour microenvironment components are therefore essential to understand drug response and resistance mechanisms. Herein, our goal was to develop a long-term OvC patient-derived explant (OvC-PDE) culture strategy in which architecture and cell type heterogeneity of the original tumour would be retained. Samples from 25 patients with distinct OvC types and one with a benign tumour, were cultured for 30 days in agitation-based culture systems with 100% success rate. OvC-PDE cultures retained the original tumour architecture and main cellular components: epithelial cells, fibroblasts and immune cells. Epithelial cells kept their original levels of proliferation and apoptosis. Moreover, the major extracellular components, such as collagen-I and -IV, were retained in explants. OvC-PDE cultures were exposed to standard-of-care chemotherapeutics agents for 2 weeks, attesting the ability of the platform for drug assays employing cyclic drug exposure regimens. We established an OvC-PDE dynamic culture in which tumour architecture and cell type heterogeneity were preserved for the different OvC types, replicating features of the original tumour and compatible with long-term drug exposure for drug efficacy and resistance studies.

Scientifc Reports