Modeling Ovarian Cancer Heterogeneity and Tumor-Stroma Crosstalk

Modeling Ovarian Cancer Heterogeneity and Tumor–Stroma Crosstalk

This internship focuses on the development and optimization of biologically relevant in vitro ovarian cancer models to better recapitulate tumor heterogeneity and tumor–microenvironment (TME) interactions. By integrating stromal and immune components into both 2D and 3D culture systems, the project aims to generate advanced preclinical platforms for evaluating standard-of-care therapies and for supporting future targeted and radiopharmaceutical strategies.
Ovarian cancer is characterized by high molecular diversity, frequent late-stage diagnosis, and substantial therapeutic resistance. Conventional 2D monoculture systems fail to capture the spatial organization, cell–cell interactions, and stromal influences that critically shape tumor behavior and treatment response. Therefore, this project addresses the need for more predictive models that reflect the complex cellular ecosystem of ovarian cancer.

Research Question
How does the interplay between fibroblasts, immune cells, and distinct molecular subtypes of ovarian cancer influence tumor growth kinetics, morphology, and biomarker expression in 2D versus 3D culture systems?

Project Objectives and Approach
The core objective of this internship is to establish and compare 2D and 3D ovarian cancer models across multiple molecular subtypes, including high-grade serous, low-grade serous, endometrioid, clear cell, and mucinous ovarian cancer. Both monocellular (homoculture) and multicellular (heteroculture) systems will be developed, incorporating cancer-associated fibroblasts (CAFs) and, where applicable, immune cells to model tumor–stroma crosstalk.
Morphological and compositional analysis of 3D spheroids will be performed using epifluorescence microscopy, enabling assessment of spheroid architecture, compaction, and stromal cell distribution. Following growth and treatment evaluation, both 2D and 3D models will undergo immunocytochemistry, immunohistochemistry, and molecular analyses (e.g. Western blotting) to characterize the expression of key ovarian cancer and microenvironment-associated biomarkers.

Expected Impact
By comparing simplified and complex preclinical models, this project will:
•    Elucidate how tumor–stroma interactions modulate therapeutic response.
•    Identify model-dependent differences in drug sensitivity and biomarker expression.
•    Establish robust, translationally relevant ovarian cancer models for therapeutic evaluation.
•    Provide a strong experimental foundation for future studies in targeted therapies and radiotheranostics.
Overall, this internship will contribute to a deeper understanding of the cellular and molecular dynamics governing ovarian cancer progression and treatment response, supporting the development of more predictive preclinical platforms and ultimately improving translational research in ovarian cancer.