Research

1. DEVELOPMENT OF CLINICALLY RELEVANT CANCER MODELS

Clinically relevant models are essential for cancer research. We have developed and characterized neuroblastoma patient-derived orthotopic xenograft (PDX) models which retain the genetic features, transcriptome profiles, protein markers, invasive growth pattern, and metastatic capacity of high-risk patient tumors (Braekeveldt et al., Cancer Res, 2018). PDX models are clinically relevant models which can be used to decipher treatment resistance and for preclinical drug testing. We further established humanized models of neuroblastoma bone marrow metastatic disease (Grigoryan et al., Sci Transl Med, 2022). The models recapitulate many of the features of bone marrow metastatic disease in neuroblastoma patients. These models will therefore be important to understand and target neuroblastoma metastasis. 

2. MECHANISMS OF METASTASIS AND RELAPSE

Current treatment of high-risk neuroblastoma includes a combination of chemotherapies, surgery, targeted therapy, anti-GD2 therapy, and more. Many patients have an initial response to treatment but treatment-resistant relapse is common. Intra- and intertumor heterogeneity are significant challenges in this context (Karlsson et al., Nature Genetics, 2018). We have shown that neuroblastoma chemoresistance is associated with an immature mesenchymal-like phenotype (Manas et al., Sci Adv, 2022). We seek to investigate the molecular mechanisms and pathways underlying neuroblastoma metastasis and treatment relapse. An integrated understanding of the genetic and non-genetic mechanisms involved in relapse is necessary to identify novel treatment regimens.

3. IDENTIFICATION OF NOVEL THERAPIES AGAINST NEUROBLASTOMA

We work to identify and test novel therapies against high-risk neuroblastoma. Using molecular characterization we aim to identify new approaches for targeting resistant tumors with novel drugs and drug combinations. We are continuously evaluating new treatments in clinically relevant patient-derived models in vitro and in vivo.