Project

Identification of Low-Grade Serous Ovarian Carcinoma (LGSOC) therapeutics using clinical relevant spheroid and tumor-engineered models for peritoneal metastasis.

Code
3F017020
Duration
01 November 2020 → 31 October 2024
Funding
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Cancer biology
    • Cancer therapy
  • Engineering and technology
    • Tissue engineering
Keywords
3D spheroid models and tumor engineered scaffolds as clinical relevant in vitro and in vivo models. Low-Grade Serous Ovarian Carcinoma and peritoneal metastasis. Tumor-microenvironment including cancer-associated fibroblasts.
 
Project description

Low-Grade Serous Ovarian Carcinoma (LGSOC) accounts for a smaller proportion of all ovarian cancer, the deadliest gynaecological cancer, and the majority of patients presents with peritoneal metastasis (PM). Standard of care therapies are not successful in improving patient outcome. There is a need of preclinical models accurately mimicking the biological properties for drug discovery. To mimic the 3D context of these PM I will implement spheroid and tumor-engineering technology that takes into account stromal elements such as cancer-associated fibroblasts (CAF). Heterocellular LGSOC spheroid models will be screened for compounds currently used in clinical trials/practise of other tumor types. Targets will be validated by RNA interference and CRISPR/Cas9 technology. Mechanistic information will be obtained by proteomics. I will 'tumor engineer' a LGSOC model that biophysically mimics PM using acrylate-terminated, urethane-based PEG (AUP) polymer. I will select the optimal PEG length whereby the stiffness, comparable to the in vivo PM, is generated by the cancer and stromal cell mass and is not imposed by scaffold characteristics. Scaffolds will be peritoneally engrafted in mice to confirm the microscopic and biophysical resemblances of in vivo PM. In conclusion, my goal is to implement tumor engineering to faithfully recapitulate PM of genetically different LGSOC. Therapeutics identified through in vitro spheroid modelling will be evaluated using this in vivo model.