A self-immolative prodrug micelle-hydrogel targets key genomic signalling pathways in PDAC metastatic model

Carlos Afonso – Professor, Instituto de Investigação do Medicamento (iMed), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.; João Conde – Professor, NOVA Medical School|Faculdade de Ciências Médicas, NMS|FCM, Universidade NOVA de Lisboa, Lisbon, Portugal; João Conniot – Researcher, NOVA Medical School|Faculdade de Ciências Médicas, NMS|FCM, Universidade NOVA de Lisboa, Lisbon, Portugal; Susete Fernandes – Researcher, i3N/CENIMAT, Department of Materials Science, NOVA School of Science and Technology, Universidade NOVA de Lisboa, Campus de Caparica, Caparica, Portugal.; Catarina Leal – Researcher, i3N/CENIMAT, Department of Materials Science, NOVA School of Science and Technology, Universidade NOVA de Lisboa, Campus de Caparica, Caparica, Portugal.; Jhenifer Oliveira – Researcher, NOVA Medical School|Faculdade de Ciências Médicas, NMS|FCM, Universidade NOVA de Lisboa, Lisbon, Portugal; João Ravasco – Researcher, NOVA Medical School|Faculdade de Ciências Médicas, NMS|FCM, Universidade NOVA de Lisboa, Lisbon, Portugal

Introduction:

Pancreatic cancer remains both one of the leading causes of cancer mortality, and one of the most lethal malignancies. Systemic chemotherapy (CT) remains the mainstay in both first-line (1 L) and second-line and beyond (2 L +) regimens in patients with locally advanced and metastatic pancreatic ductal adenocarcinoma (PDAC) without actionable genomic alterations. The introduction of targeted therapies has significantly improved the outcomes of many patient populations across several solid and hematologic tumours, however, these have shown limited clinical benefit in PDAC.