TGF-beta and cancer

Summary

The research group's focus is on studying the dual role of transforming growth factor (TGF)-β in regulating the initiation and progression of liver cancer, as well as deciphering the relevance of other signaling pathways that interact with it, particularly the epidermal growth factor (EGF). In recent years, we have made progress in studying the TGF-β signaling pathway and have identified the production of reactive oxygen species (ROS) mediated by the NADPH oxidase family, particularly NOX4, as a key element in TGF-β function.

Currently, we are working on advancing in:

the role of TGF-β and oxidative stress in the tumor microenvironment;
identifying new targets related to TGF-β or redox stress to guide the search for novel therapeutic strategies for liver cancer;
analyzing which patients may benefit from TGF-β pathway inhibition to improve the response of hepatocellular carcinoma to immunotherapy.

268 Publications

Strategic lines

Molecular mechanisms involved in the regulation of liver regeneration, fibrosis, and cancer, with a focus on the role of TGF-β and the EGF receptor pathway in these processes.
Function of the NADPH oxidase (NOX) family as mediators of TGF-β effects. Regulation of metabolism and cellular redox balance through the TGF-β/NOX4 axis.
Tumor-stroma interaction in tumor initiation and progression: role of TGF-β in both tumor cells and the stroma. Evaluation of the therapeutic potential of TGF-β inhibitors in liver cancer.

Selected Publications

Iron chelation as a new therapeutic approach to prevent senescence and liver fibrosis progression. Amengual J, Alay A, Vaquero J, Gonzalez-Sanchez E, Bertran E, Sánchez A, Herrera B, Meyer K, Maus M, Serrano M, Martínez-Chantar ML, Fabregat I.Cell Death Dis. 2024 Sep 17;15(9):680. doi: 10.1038/s41419-024-07063-0.PMID: 39289337
PRRX1 silencing is required for metastatic outgrowth in melanoma and is an independent prognostic of reduced survival in patients. Ferreres JR, Vinyals A, Campos-Martin R, Espín R, Podlipnik S, Ramos R, Bertran E, Carrera C, Marcoval J, Malvehy J, Fabregat I, Puig S, Fabra À.Mol Oncol. 2024 Oct;18(10):2471-2494. doi: 10.1002/1878-0261.13688. Epub 2024 Jul 8.PMID: 38978350
The hepatocyte epidermal growth factor receptor (EGFR) pathway regulates the cellular interactome within the liver fibrotic niche. Gonzalez-Sanchez E, Vaquero J, Caballero-Diaz D, Grzelak J, Fusté NP, Bertran E, Amengual J, Garcia-Saez J, Martín-Mur B, Gut M, Esteve-Codina A, Alay A, Coulouarn C, Calero-Perez S, Valdecantos P, Valverde AM, Sánchez A, Herrera B, Fabregat I.J Pathol. 2024 Aug;263(4-5):482-495. doi: 10.1002/path.6299. Epub 2024 Jun 14.PMID: 38872438
Dissecting the role of the NADPH oxidase NOX4 in TGF-beta signaling in hepatocellular carcinoma. Espinosa-Sotelo R, Fusté NP, Peñuelas-Haro I, Alay A, Pons G, Almodóvar X, Albaladejo J, Sánchez-Vera I, Bonilla-Amadeo R, Dituri F, Serino G, Ramos E, Serrano T, Calvo M, Martínez-Chantar ML, Giannelli G, Bertran E, Fabregat I.Redox Biol. 2023 Sep;65:102818. doi: 10.1016/j.redox.2023.102818. Epub 2023 Jul 13.PMID: 37463530
The NADPH oxidase NOX4 regulates redox and metabolic homeostasis preventing HCC progression. Peñuelas-Haro I, Espinosa-Sotelo R, Crosas-Molist E, Herranz-Itúrbide M, Caballero-Díaz D, Alay A, Solé X, Ramos E, Serrano T, Martínez-Chantar ML, Knaus UG, Cuezva JM, Zorzano A, Bertran E, Fabregat I.Hepatology. 2023 Aug 1;78(2):416-433. doi: 10.1002/hep.32702. Epub 2022 Sep 17.PMID: 35920301

Selected Projects

MCI21045. Descifrando el papel de la NADPH oxidasa NOX4 en el carcinoma hepatocelular: relevancia en células tumorales y estroma y relación con la vía del TGF-beta. Ministerio de Ciencia e Innovación. Budget: 344.850€. 2022-2025. PI: FABREGAT ROMERO, MARIA ISABEL.
AEC21009. Towards a precision medicine using TGF-ß inhibitors in hepatocellular carcinoma and cholangiocarcinoma. Asociación Española Contra el Cáncer (AECC). Budget: 299.813,75€. 2021-2025. PI: FABREGAT ROMERO, MARIA ISABEL.
21PSJ005. Dissecting the role of the hepatocyte Epidermal Growth Factor Receptor (EGFR) pathway in the cellular interactome within the liver fibrotic niche. FUNDACIÓN RAMÓN ARECES. Budget: 112.000€. 2021-2024. PI: FABREGAT ROMERO, MARIA ISABEL.
2022-040-1. PRIMER ESTUDIO DE FASE I EN HUMANOS, SIN ENMASCARAMIENTO, DE AUMENTO ESCALONADO DE LA DOSIS PARA EVALUAR LA SEGURIDAD, LA FARMACOCINÉTICA, LA FARMACODINÁMICA Y EL PERFIL DE ACTIVIDAD CLÍNICA PRELIMINAR DEL AGENTE RO7119929 (AGONISTA DE TLR7) EN MONOTERAPIA ADMINISTRADO POR VÍA ORAL A PARTICIPANTES CON CARCINOMA HEPATOCELULAR AVANZADO IRRESECABLE O METASTÁSICO, CÁNCER DEL TRACTO BILIAR O TUMORES SÓLIDOS CON METÁSTASIS HEPÁTICAS. FORTREA INC. Budget: 193.971€. 2022- . PI: Calvo Campos, Mariona.