2020 June 11

Evaluation of new targeted therapies in aggressive B-lymphomas.

The Lymphoma Translational Research Group is developing in vitro and in vivo assays to characterize new antineoplastic drugs against Diffuse Large Cell Lymphoma (DLCG), Mantle Cell Lymphoma (MCL) and Transformed Follicular Lymphoma (TFL), in the FIS project Nº PI18/01383 financed by the Instituto de Salud Carlos III.

Aggressive B-cell lymphomas are clinically and pathologically diverse and reflect multiple pathways of transformation. In parallel to the alterations of specific oncogenes (MYC, BCL6) the overexpression and constitutive activation of the BCR and PI3K pathways, the ubiquitin-proteasome system, and antiapoptotic factors of the BCL-2 family play a vital role in the progression of malignant clones and their interaction with the lymphoid microenvironment and are related to a high failure rate in treatment protocols.

To design new therapies that are more selective and more in line with the biology of these lymphomas, the Translational Lymphoma Research group led by Gael Roué has undertaken the FIS PI18/01383 project "Development of a platform of patient-derived xenografts for the evaluation of new targeted therapies in aggressive B-cell lymphomas." This project focuses on the characterization of new antineoplastic drugs capable of specifically interfering with these factors, in in vitro and in vivo models of diffuse large cell lymphoma (DLCG), mantle cell lymphoma (MLC) and follicular transformed lymphoma (TFL). To guarantee the efficacy, safety, and translationality of these studies, researchers will mainly assess the therapeutic potential of these agents in combination with conventional therapies (R-CHOP, bortezomib, ibrutinib, idelalisib) using new murine models of patient-derived xenografts (PDX) of each lymphoma subtype.

The research includes the analysis of therapeutic compounds developed and validated by pharmaceutical companies and recognized academic groups, and the molecular and genetic characterization of the factors that determine the efficacy of each treatment in a series of primary samples; an extensive panel of cell lines representative of each entity; and preclinical transgenic, systemic and xenotransplantation models of LCM, LDCG, and LFt.