Research Lines

Pediatric tumors of the nervous system are the most common solid malignant neoplasms of childhood cancer and the leading cause of cancer-related death in children. 

The main objective of our laboratory is to implement the use of epigenetic therapies, that is, therapies against gene expression modulators that, in turn, regulate several genes, pathways or cellular processes, without affecting the DNA sequence. The laboratory focus on neuroblastoma, a pediatric solid tumor of the peripheral nervous system, and on pediatric brain tumor of the central nervous system pediatric such as ependymoma, medulloblastoma or high-grade glioma among others.

Metastatic relapse is the major cause of death in neuroblastoma. The liver, bone and bone marrow and lymph nodes are among the most common metastatic sites of neuroblastoma patients, which constitute a “reservoir” of tumor cells that persistently reside in patients following local and systemic cancer therapy. Their elimination continues to represent the most difficult challenges for neuroblastoma patients. Our hypothesis is that metastatic cells can colonize distant organs thanks to the re-organization of their epigenetic landscape. Results of the last five years of the laboratory clearly shows that chromatin remodelers may play significant role in the aggressiveness of neuroblastoma. Therefore, in this cell line we are i) Characterizing the epigenetic landscape of metastatic neuroblastoma; ii) Characterizing the transcriptomic map of chromatin remodelers (i.e. SWI/SNF)-regulated genes in neuroblastoma metastasis; iii) Developing of an epigenetic therapy based on the inhibition of chromatin remodeling complexes; iv) Developing more sensitive tools to diagnose and target neuroblastoma metastasis. 

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. 

Pediatric tumors of the central nervous system (CNS) are the most common solid malignancies in children, second only to hematologic malignancies, and are the leading cause of cancer-related deaths. Epigenetic therapies aimed at reversing the oncogenic alterations in chromatin structure and function are an emerging alternative against aggressive tumors that are or will become resistant to conventional treatments. This research line constitutes an effort to identify the addiction of pediatric brain tumors to epigenetic regulators (e.g. chromatin remodelers, histone deacetylases, etc) and develop new epigenetic drugs. Furthermore, we are also elaborating a roadmap for the implementation of immunotherapies in pediatric brain tumors and characterizing the role of the tumor microenvironment in the aggressiveness of these tumors.

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

RNA-based therapies may represent a paradigm shift for the treatment of neuroblastoma, or cancer in general, because they have the potential to act on the entire transcriptome, thus expanding the number of drug targets, since they could modulate both RNA coding (2% of the total genome that is transcribed) and non-coding RNAs (80% of the genome that is transcribed). Within RNA-based therapies, the most advanced molecules from a clinical development point of view are small RNAs (e.g. siRNA or microRNA). One of our working hypothesis is that the microRNAs (miRNAs) deregulation is contributing to the metastatic and chemoresistant behavior of high-risk neuroblastoma and miRNA(s) levels restoration represents an attractive novel therapeutic approach.

 -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