Daniel Torralba Maldonado postdoctoral scholarship hold.

Research Daniel Torralba Maldonado

Research team

Expertise

My research expertise lies in organic and medicinal chemistry, with a particular focus on the design, synthesis, and characterization of bioactive molecules and enzyme-responsive systems for cancer therapy. My work focuses on the development of targeted drug delivery strategies using chemotherapeutic agents and self-immolative linkers that can be selectively activated in the tumour environment. In particular, I work on systems targeting Fibroblast Activation Protein (FAP), an enzyme overexpressed in the tumour microenvironment, as well as cathepsins, which are highly present in tumour tissues. My research includes the development of fluorogenic probes, prodrugs, and enzyme-cleavable systems aimed at improving selectivity and reducing off-target toxicity. I collaborate in interdisciplinary projects combining synthetic chemistry, chemical biology, and biological evaluation for the development of novel therapeutic approaches in oncology.

Dual-targeted KetoFAPI Conjugates for Tumor-Selective Bimodal Therapy in Triple-Negative Breast Cancer (BiFAP). 01/04/2026 - 31/03/2028

Abstract

Triple-negative breast cancer (TNBC) remains one of the most aggressive subtypes of breast cancer, with limited therapeutic options and a poor prognosis. To offer dearly needed new treatment perspectives, we want to target fibroblast activation protein (FAP), a protease that is highly expressed on cancer-associated fibroblasts (CAFs) in tumors but negligible in most healthy tissue. Building on this rationale, the host institution has pioneered novel ketoFAPIs, small-molecule FAP inhibitors with exceptionally long tumor residence times, providing a unique opportunity to design advanced drug delivery platforms. This project will exploit the unique properties of ketoFAPIs to design bimodal conjugates that combine chemotherapy and radionuclide therapy in a single, tumor-targeted platform. These conjugates will integrate: (i) a ketoFAPI as the primary targeting moiety, (ii) a DOTAGA chelator for radionuclide labeling, and (iii) a cleavable linker for selective intratumoral release of potent chemotherapeutics such as MMAE or SN-38. To further enhance tumor selectivity and reduce bone marrow toxicity, a dual-targeting strategy will be pursued by adding folic acid as a second tumor-binding ligand. The project is structured into three objectives: 1) synthesis and characterization of Type I and II conjugates, 2) in vitro validation of efficacy and selectivity in TNBC organoid models, 3) in vivo evaluation of biodistribution, tumor uptake, and bone marrow safety in TNBC mouse models. By integrating long-residence FAP targeting with dual-modality therapy and dual-ligand selectivity, this research introduces a first-in-class therapeutic strategy for TNBC. Expected outcomes are optimized conjugates with enhanced tumor selectivity, reduced hematological toxicity, and improved therapeutic potential. Aligned with the EU's Beating Cancer Plan, this project directly addresses the need for innovative, tumor-targeted therapies to improve cancer patient survival and quality of life.

Researcher(s)

Research team(s)

Funding

  • EU-KADER

Project type(s)

  • Research Project