Learn More About Our Projects
Tumor heterogeneity comprehension for an improved diagnosis and treatment choice for TNBC
Triple-negative breast cancer (TNBC) is a highly heterogeneous disease lacking well-defined biomarkers, which limits patient stratification and therapeutic decision-making. Although patients are classified under the same clinical subtype, their tumors can differ substantially in cellular composition, leading to variable treatment responses and clinical outcomes. To address this challenge, we investigated the cellular heterogeneity of TNBC tumors with the aim of identifying novel biomarkers and therapeutic targets. By characterizing distinct tumor cell populations, we sought to better define which cells are more likely to respond to current treatments or contribute to metastasis. Our work has contributed to a more refined understanding of TNBC heterogeneity and supports the development of personalized strategies, enabling more patients to be considered for targeted therapies.
People involved: Daniel Ortega, David Tébar, David Olivares, Cristina Guardia, Elena Castillo, Joan Balibrea, Elena Vinuesa.
Collaborators: Mireia Margelí, MD; Pedro L. Fernández, MD; Elisabetta Mereu, PhD; Ginés Luengo, PhD; Eva M. Galan-Moya, PhD
Funding agencies: Asociación Española Contra el Cáncer AECC
Project Progress
Key Outputs
PhD Thesis: Daniel Ortega (2025)
Disrupting senescence-mediated survival pathways in primary lymphomas
While the R-CHOP chemotherapy regimen is effective in targeting proliferative lymphoma cells, a subset of tumor cells can enter a drug-persistent state, allowing them to survive initial treatment and later drive relapse. In this project, we aim to identify and target the vulnerabilities of these persistent cells at the primary tumor site. We hypothesize that senescent cells, induced by R-CHOP in the tumor microenvironment, contribute to the survival and awakening of drug-persistent cells through paracrine signals. Targeting these interactions may prevent reactivation of minimal residual disease. Our objectives are identifying senescence-associated surface biomarkers in NHL and developing membrane-targeted therapeutic strategies to prevent the awakening of persistent cells. We use molecular profiling and functional assays to explore the interactions between senescent and persistent tumor cells.
People involved: Joan Balibrea, Cristina Guardia, David Olivares
Funding agencies: ASEICA +queuntrail; Fundació Jané Mateu
Project Progression
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Therapy-induced senescence in NHL relapses
In the cancer context, senescence has been repeatedly considered as a tumor suppressor mechanism. However, accumulating evidence has indicated that senescent cells can also have a pro-tumorigenic role. Specifically, the inhibition of factors secreted by these cells resulted in reduced tumor growth, supporting the idea that senescent cells contribute to tumor progression in advanced stages of the disease. Importantly, several chemotherapies and radiotherapies, which are designed to specifically target proliferating cells, can induce senescence systemically. Our main objective is to generate in vitro and in vivo tools that allow us to know whether senescent cells could work as a therapeutic target against relapse in non-Hodgkin lymphoma.
People involved: Cristina Guardia, Basseem Radwan, Joan Balibrea, Mariia Sydorenko, David Olivares
Collaborators: Tomás Navarro, MD and Elisabetta Mereu, PhD
Funding agencies: Fundació Josep Carreras
Project Progression
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Defining new biomarkers for breast cancer
A major challenge in breast cancer research is the disease's heterogeneity. Two patients with the same cancer type can have vastly different cellular compositions, making it impractical to select identical treatments for both. With this project, we aim to identify reliable human biomarkers for the three types of mammary epithelial cells, which allow us to subclassify tumors more precisely. Based on analysis of single cell RNA-sequencing combined with the use of human breast cancer samples, we will be able to refine the diagnosis of different breast cancer subtypes.
People involved: David Olivares, Daniel Ortega, Elena Castillo, Eva Musulén
Collaborators: Joaquín Arribas
Funding agencies: Fundación FERO with the contribution of ghd
Project Progression
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Tracing the cellular origin of breast tumors
Studies based on lineage tracing experiments have shown that the mammary gland epithelium is self-maintained by three independent cellular populations: luminal ER-negative, luminal ER-positive and basal cells. Interestingly, upon different stressful situations such as transplantation, oncogene activation or cellular ablation adult committed cells can de-differentiate acquiring multipotent capacity in vivo. This project aims to examine whether multipotent stem cells are present in breast tumors by monitoring the three different mammary cell compartments separately in different murine breast cancer models. We believe that elucidating the genetic signatures underlying cellular identity, lineage commitment, and cellular plasticity will enhance our understanding of breast cancer heterogeneity.
People involved: Elena Vinuesa, Daniel Ortega, David Olivares, Lidia Soto
Funding agencies: RETOS I+D 2020; PIF-SALUT 2021-2024 (PERIS)
Project Progression
Funding Agencies
