


Title
Using lymphatic vessels to strategically target pancreatic ductal adenocarcinoma (LYMPDAC)
Using lymphatic vessels to strategically attack pancreatic ductal adenocarcinoma (LYMPDAC)
Description
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide due to its rapid progression to an aggressive stage and the lack of effective therapies. PDAC aggressiveness is driven by intense fibroblast desmoplastic reaction that together with collapsed and leaky blood vessels leads to fluid accumulation generating a high interstitial fluid pressure (IFP). The elevated IFP is correlated with higher PDAC metastasis outcome. Strategies targeting cancer associated fibroblasts in PDAC have been so far counterproductive. Lymphatic vessels (LVs) that in PDAC are sparse and dysfunctional are crucial to drain the fluid from the tumor insterstitium.
Objectives and Results
Here, the aim is to make a crossroad of mechanobiology and cellular biology to target PDAC. By inducing PDAC intratumoral formation of LVs a lower IFP will be achieved. This new mechanoenvironment will favor the delivery of chemo and angio/immunotherapies. This objective will be achieved by using a new and innovative technique, the use of microfluidic devices together with a robust in vivo mouse model of PDAC.
This study will be vital for advancing the fundamental understanding of the complex PDAC tumor microenvironment and will open new avenues to make effective therapies for PDAC patients. Importantly, the combination of biomechanics and cancer cell biology will entail new horizons for cancer therapeutics. Furthermore, given the existence of organ-specific vascular organization, the modulation of LVs in a solid tumor different to subcutaneous melanoma or breast cancer models is a challenge nowadays and will uncover clinically relevant outputs.
IP IIS Aragon
Dr. Alejandra González Loyola
Supervisors: Dr. Patrícia Sancho Andrés, Dr. José Manuel García Aznar.
Financing Agency
Financed by the Carlos III Health Institute with European funds from the Recovery, Transformation and Resilience Plan, with file code IHMC22/00004 (“Using lymphatic vessels to strategically target pancreatic ductal adenocarcinoma”), by virtue of the Resolution of the Directorate of the Carlos III Health Institute, OA, MP of December 22, 2022, by which “ISCIII Seal of Excellence” subsidies are granted. HEALTH”, and “Funded by the European Union – NextGenerationEU".
Coordinator
Alejandra González Loyola
Be a partner
Not applicable
Duration
20/06/2023 – 19/06/2025 (24 months)
Web
Not available