Meritxell B. Cutrona is a cell biologist with a primary interest in membrane trafficking research at a fundamental level and applied to the development of screening for innovative therapies using 3D cancer cell culture models. In recent years, she has gained extensive experience in high-content screening microscopy applied to functional (phenotypic) profiling of chemoresistance, drug discovery and precision medicine. Her work focuses on the development and application of advanced high-throughput screening platforms for 3D cell culture models, including spheroids, and patient-derived tumour organoids, with a particular interest on pancreatic cancer. Her research bridges cutting-edge screening technology, molecular and cellular oncology, functional genomics, and preclinical drug discovery, with the goal of uncovering novel and personalized, therapeutic vulnerabilities, to improve translational relevance in cancer models.

Her recent research contributions on tumour organoid-based high-content drug screening span several high-impact studies.  For example, in her iScience article, “Pancreatic cancer organoid-screening captures personalized sensitivity and chemoresistance suppression upon cytochrome P450 3A5-targeted inhibition” (https://doi.org/10.1016/j.isci.2024.110289), Cutrona, Taosheng Chen and colleagues used patient-derived pancreatic cancer organoids for high content screening to profile responses to CYP3A5 inhibition with clobetasol propionate. They found that drug sensitivity correlated with CYP3A5 expression levels and that inhibition could restore cisplatin responsiveness in resistant models. Proteomic analysis further showed suppression of mutant p53–associated pathways, supporting CYP3A5 as a target for overcoming chemoresistance and enabling more personalized treatment strategies in pancreatic cancer.

Under her direction of an HTS Facility, and in close collaboration with the group of Prof. Stephanie Kries at the University of Luxembourg, she contributed to design and deploy a screen of over 1,300 FDA-approved compounds in 3D spheroid models of NRAS-mutant melanoma. The paper “High-throughput drug screening in advanced pre-clinical 3D melanoma models identifies potential first-line therapies for NRAS-mutated melanoma” (https://doi.org/10.21203/rs.3.rs-6594118/v1), reports two repurposed drugs, Daunorubicin HCl and Pyrvinium Pamoate, which showed potent anti-melanoma activity in spheroids as validated in co-culture systems mimicking three metastatic sites and in zebrafish xenografts. This work underlines the power of combining physiologically relevant 3D cancer models with high-throughput screening followed by hit validation in vivo, to identify new first-line therapy options for melanoma subtypes with few targeted options.

As the Head of the Organoid Core Facility at Gustave Roussy in France, she has contributed to establish primary organoid lines using adult stem cell technology for sarcoma, as well as to design and apply drug-drug combination testing using high-content screening. As part of HCS-driven validation with sarcoma she contributed to demonstrate that a combination of PARP and ATR inhibitors may provide an effective therapeutic strategy for an aggressive sarcoma subtype linked to the EWS–WT1 fusion organoids as reported in the Cancer Research article “Replication Stress Is an Actionable Genetic Vulnerability in Desmoplastic Small Round Cell Tumor” (https://doi.org/10.1158/0008-5472.CAN-23-3603). The study highlights replication stress as a targetable vulnerability in DSRCT and provides strong rationale for clinical evaluation of PARP and ATR inhibitors in patients.

Through her multidisciplinary expertise, ranging from 3D tumor modeling to functional screening and molecular characterization, Meritxell B. Cutrona has advanced our understanding of cancer heterogeneity and therapeutic response, with a strong emphasis on clinically relevant systems that better predict patient outcomes and enable advanced anti-cancer drug discovery.

Don’t miss Meritxell B. Cutrona’s session on September 30th to dive deeper into her latest findings.