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- Deciphering Biology of R/R DLBCL Subtypes: miRNA Biomarkers for Optimizing Treatment and Survival
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- Developing a Biobank Network Among Major Sarcoma Treatment Centers to Improve Biomedical Research
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- Exploring the role of Bcl-2 family in the immune surveillance of melanoma: from mechanisms to therapeutic perspectives
- Exploring how endothelin-1/PIEZO axis intersects mechanical forces to fuel PARP inhibitor resistance in ovarian cancer
Deciphering the biology of relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) subtypes: Identification of predictive biomarkers including miRNA-based tumor signatures to optimize sequential treatment decisions towards the effective improvement of patient long-term survival
Project description
PI: Stefan Hohaus – IRCCS Fondazione Policlinico Universitario A. Gemelli
IRE Principal Collaborators Involved:Maria Rizzo, Francesco Marchesi, Gianluca Bossi, Giulia Regazzo, Rossella Loria
Project duration: 24 months
Project code: PNRR-MAD-2022-12376707
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, accounting for 30-40% of cases. While the standard R-CHOP therapy cures 55-60% of patients, about 15% are primary refractory and 25-30% relapse, usually within 24 months. Relapsed/refractory DLBCL (R/R DLBCL) remains an unmet medical need, with limited success from conventional salvage therapies. However, emerging immunotherapies, including CAR-T cells and bispecific antibodies, offer promising results.
DLBCL is biologically heterogeneous, comprising subtypes with distinct molecular and immunological characteristics, influencing treatment sensitivity and resistance patterns. This project aims to decipher the biology of R/R DLBCL subtypes by identifying predictive biomarkers, including miRNA-based tumor signatures, to optimize sequential treatment decisions.
The study will employ a comprehensive approach, integrating miRNA expression profiling, genomic and epigenetic analyses, and immunotherapy-actionable tumor antigen identification through flow cytometry. It aims to correlate molecular profiles with clinical outcomes, enabling the development of predictive models for treatment response and survival.
Purpose
The primary purpose of this project is to identify and validate predictive biomarkers for R/R DLBCL to guide sequential treatment decisions. The goal is to enhance therapeutic strategies, tailoring treatments based on individual tumor biology and improving long-term patient survival. This personalized approach aims to maximize treatment efficacy while minimizing resistance and adverse effects.
Expected Outcomes
Identification of Biomarkers: Discovery and validation of miRNA-based tumor signatures and other predictive biomarkers to classify R/R DLBCL subtypes.
Predictive Models: Development of predictive models for treatment response and patient survival, integrating molecular profiles with clinical data.
Personalized Treatment Strategies: Optimization of sequential treatment decisions, enabling personalized therapeutic approaches for R/R DLBCL patients.
Clinical Impact: Improvement in long-term survival rates, enhanced quality of life, and reduced healthcare burdens for DLBCL patients.
Scientific Advancement: Increased understanding of the molecular mechanisms driving DLBCL relapse and resistance, paving the way for future biomarker discoveries and innovative therapeutic strategies.
Financial Support
PNRR, financed by Ministero della Salute
The total grant of the project is: € 1.000.000,00
The grant assigned to IFO – IRE is: € 290.000,00
Other Institution involved: IRCCS Fondazione Policlinico Universitario A. Gemelli, Istituto Nazionale Tumori, Fondazione "G. Pascale" IRCCS
The funding resources are from the public notice Avviso pubblico per la presentazione e selezione di progetti di ricerca da finanziare nell’ambito del PNRR sulle seguenti tematiche:
- Proof of concept (PoC);
- Malattie Rare (MR);
- Malattie Croniche non Trasmissibili (MCnT) ad alto impatto sui sistemi sanitari e socio-assistenziali:
- Fattori di rischio e prevenzione,
- Eziopatogenesi e meccanismi di malattia
Piano Nazionale di Ripresa e Resilienza - Missione M6 - Componente C2 - Investimento 2.1 Valorizzazione e potenziamento della ricerca biomedica del SSN finanziato dall’Unione europea - NextGenerationEU.