Lymphoproliferative syndromes (LS) are a group of hematological malignancies characterized by proliferation of neoplastic mature lymphocytes. Among LS, B-cell non-hodgkin lymphomas (B-NHLs) represent 40% of all hematological malignancies and comprise a varied group of more than 20 unique subtypes that are routinely classified according to clinical, histopathological and genetic features. As prominent examples, we focus our research to diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), marginal-zone lymphoma (MZL) and Waldenstrom macroglobulinemia (WM), which we study by using multidisciplinary approaches and close collaboration between basic and clinical researchers at CIMA and Clínica Universidad de Navarra.
The biological heterogeneity within each lymphoma subtype is hampering the successful demonstration of novel targeted therapies in clinical trials and, therefore, advances in such therapeutic strategies will require an improved understanding of the fundamental biology of each lymphoma entity with the aim of defining optimal drug combinations for specific groups of patients. Furthermore, the interactions between lymphoma cells and microenvironmental cells in the lymph node, bone marrow and other lymphoid tissues have also been found to be critical in lymphoma pathogenesis and, accordingly, it is expected that such tumor-microenvironmental cell dependencies will disclose novel therapeutic interventions.
Development of genetically engineered and immunocompetent mouse models (GEIMMs) that recapitulate the complex heterogeneity of the common B-NHLs has been limited so far. Given the number of novel targeted agents in pre-clinical and clinical development, particularly with the promising perspectives of combining targeted agents and immunotherapy strategies, there is a clear need to prioritize drug combinations targeting selective driver pathways to be tested in well-established GEIMMs of B-NHLs that could potentially allow predictive guidance for patient treatment.
Our main objectives are the following:
Objective 1. Determine the cellular and molecular features underlying B-cell lymphoma and plasma-cell tumor development in genetic mouse models, defining similarities with human disease.
Objective 2. Assess pre-clinically in vivo anti-tumor efficacy of patient´s standard of care treatment alone and in combination with other immunotherapeutic and targeted agents.
Objective 3. Dissect mechanisms of therapeutic response and resistance based on characterization of tumor and microenvironment cells
Fecha de actualización: Noviembre 2018
Papel de la proteína homeobox NKX2-3 en la biología y terapia de los linfomas B de la zona marginal
Convocatoria: Proyectos de I+D en Salud. AES 2016
Título: “Papel de la proteína homeobox NKX2-3 en la biología y terapia de los linfomas B de la zona marginal”
I. P.: José Ángel Martínez Climent
Duración: 3 años
F. Inicio: 01/01/2017 F. Fin: 31/12/2019
Financiado: Por el Instituto de Salud Carlos III y cofinanciado por el Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa”.