Project Title: Role of ECM composition and stromal cells in determining tumour and cancer stem cell pH/O2 handling and therapeutic response

Objectives: Design humanized 3D models of the PDAC tumor-stroma interaction by co-culturing tumor cells (including cancer stem cells) with CAFs and macrophages in bioengineered scaffolds mimicking the desmoplastic progression. In these models, we will characterize how the changing stroma (ECM composition/stiffness, alternating pHe and O2 levels) affects (i) cell growth and invasion (ii) their de/differentiation properties and their (ii) drug response and, vice versa, how these stromal-evoked cell activities mutually support the above stromal changes. Lastly, these 3D patient-derived models will be integrated with clinical information to define novel therapeutic strategies that can be quickly translated to the clinic.