Research Lines

Epigenetics determines which genes are turned on or off without altering the DNA sequence, largely by controlling how DNA is packaged within the cell. A key player in this process is the BAF complex, a chromatin remodeler that neuroblastoma cells rely on to sustain proliferation and metastatic potential. Recent work in our laboratory has identified ARID1A/ARID1B as a promising vulnerability within the BAF complex, and this opened up two new research branches: (1) The development of small molecules to disrupt this dependency and inhibit tumor growth and (2) the use of PROTACs and specific inhibitors of SMARCA4 as a synthetic lethality strategy for ARID1A/B mutated patients.

Funding: Ref. 2024 PROD 00054. Targeting chromatin remodelers for cancer therapy.

Approximately half of neuroblastoma patients present with metastatic disease at diagnosis, most frequently involving bone, bone marrow, lymph nodes, liver, and lungs, being metastatic relapse the leading cause of death of the disease. Increasing evidence indicates that epigenetic deregulation plays a critical role in neuroblastoma initiation, progression, and metastatic dissemination. We therefore hypothesize that systematic characterization of chromatin architecture alterations and therapeutic targeting of epigenetic vulnerabilities will advance our understanding of neuroblastoma metastasis and uncover novel therapeutic opportunities.

Funding: Ref .PI23/01144  Exploiting epigenetic vulnerabilities in metastatic neuroblastoma. Instituto de Salud Carlos III. PI: Miguel F. Segura; Fundación Neuroblastoma, "Por Leire" initiative.

We are interested in testing the therapeutic potential of new synthetic or natural compounds which can represent clear advantages (i.e. increased effectiveness, reduced toxicities) compared to traditional chemotherapy. We have a clinically representative panel of pediatric solid tumor cell lines and preclinical mouse models to test the efficacy and safety of new drugs aimed to improve the efficacy and safety of currently available treatments. Currently, we are evaluating the therapeutic potential of ABTL0812 in pediatric tumors, both preclinically but also in a “first in child” Phase I clinical trial. 

Funding: Ref. ICI21/00076- A phase I trial of ABTL0812 in paediatric patients with advanced cancer including neuroblastoma.  PI: Lucas Moreno. 

Scientific Officer: Miguel F. Segura; Asociación NEN. 

Because pediatric brain tumors are the most common solid malignancies in children and still have limited treatment options resulting in poor overall survival, one of the laboratory’s main objectives is to develop new therapeutic strategies for these tumors. To this end, we are generating novel preclinical models of pediatric ependymoma to better recapitulate tumor biology and support translational research and evaluating the therapeutic potential of novel experimental compounds in vitro, including SWI/SNF inhibitors currently explored in our neuroblastoma research lines. Moreover, we aim to advance immunotherapy in pediatric brain tumors by identifying tumor-specific membrane proteins that can serve as targets for the development of more precise and effective therapeutic strategies.

Funding: -Ref: JDC2022-048237. Unveiling the role of chromatin remodelers in pediatric tumors of the central nervous system. PI: Miguel F: Segura; Pulseras Candela, Fundació Amics Joan Petit, FADAM

Liquid biopsy is a minimally invasive approach that enables the analysis of tumor-derived material in biofluids such as blood. In this project, we investigate circulating tumor DNA (ctDNA) as a biomarker for the molecular characterization and clinical monitoring of pediatric brain tumors and neuroblastoma. ctDNA analysis can provide clinically relevant information on tumor burden, tumor-associated genetic alterations, and disease dynamics over time. By allowing serial sampling, this strategy offers an attractive alternative to repeated invasive procedures. Our aim is to evaluate the potential of ctDNA to improve diagnosis, support treatment monitoring, and enable earlier detection of relapse. Ultimately, this work seeks to advance more precise, dynamic, and less invasive approaches for the management of pediatric malignancies.

-Ref. PI20/00530: Nanotools for the treatment of metastatic neuroblastoma. PI: Miguel F. Segura; Ref: 2021-PROD-00059.RNA-based nanomedicine for cancer therapy. PI: Miguel F. Segura. Fundació Amics Joan Petit