Bioengineered 3D models of pancreatic cancer as personalized medicine platforms

L de Lara-Peña(1,3,4,5) J López de Andrés(1,3,4,5) C Griñán-Lisón(1,2,3,4,5) F Martín(2) G Jiménez(1,3,4,5) J A Marchal(1,3,4,5)

1:Universidad de Granada; 2:GENyO- Centro de Genomica e Investigacion Oncologica: Pfizer / Universidad de Granada / Junta de Andalucia; 3:Biopathology and Regenerative Medicine Institute (IBIMER),; 4:Biosanitary Investigation Institute (Ibs.GRANADA); 5:Excellence Research Unit “Modelling Nature” (Mnat)

Pancreatic cancer (PC) represents the seventh leading cause of cancer death worldwide and its incidence is increasing every year. Survival in this type of tumor is less than 5% due to lack of early diagnosis, rapid disease progression, high rate of metastasis and treatment failure. In PC, the stroma constitutes more than 90% of the tumor mass and is composed of many different elements. This highlights the need to create new 3D in vitro models incorporating the tumoral microenvironment (TME), as tumor progression and response to treatments depend to a large extent on it. These models may help us to understand and overcome the resistance of PC to several therapeutic strategies. Thus, the incorporation of dECM-based bioinks provides 3D models of a more physiological TME, giving them their characteristic complexity and allowing interactions between cells and with the ECM. This makes it possible to mimic characteristics of native tumors: development and metastasis, and treatment outcomes. In addition, organoids are good personalized medicine platforms, useful in pharmacotyping studies because they show parallel sensitivity and resistances in patients. Some treatments strategies, as CAR-T therapy, find many challenges to be effective in solid tumors. Because PC organoids can mimic the native tissue, they can facilitate the identification of novel antigens which could serve as targets for CAR-T therapy and also can help us to better understand resistance to it.