ESTRO 2024 - Abstract Book

S5404

Radiobiology - Tumour biology

ESTRO 2024

ROCK1 is required for the DDR in response to IR and nuclear translocation of ROCK1 immediately after IR. ROCK1 participates in DNA repair via the NHEJ pathway by phosphorylation of Ku70 at serine 477, allowing the Ku protein complex to activate DNA-PKcs during NHEJ. Lacking ROCK1 or inhibition of ROCK1 activity results in impaired DNA damage repair and enhanced radiosensitivity. ROCK1 is a key regulator of DNA damage repair provides new insights into its role in the DDR and highlights the potential of ROCK1 as a target for molecular radiosensitization.

Keywords: ROCK1, non-homologous end joining, XRCC6/Ku70

2302

Mini-Oral

Development of Pancreatic Ductal AdenoCarcinoma on-chip for radiobiological applications

Luca Possenti 1 , Sofia Tartaro 2 , Chiara Arrigoni 3,4 , Nadia Zaffaroni 5 , Matteo Moretti 3,4,6 , Tiziana Rancati 1

1 Fondazione IRCCS Istituto Nazionale dei Tumori, Data Science Unit, Milan, Italy. 2 Politecnico di Milano, Department of Chemistry, Materials and Chemical Engineering, Milan, Italy. 3 Ente Ospedaliero Cantonale, Regenerative Medicine Technologies Lab, Service of Orthopaedics and Traumatology, Bellinzona, Switzerland. 4 Università della Svizzera Italiana (USI), Euler Institute, Biomedical Sciences Faculty, Lugano, Switzerland. 5 Fondazione IRCCS Istituto Nazionale dei Tumori, Molecular Pharmacology Unit, Milan, Italy. 6 IRCCS Istituto Ortopedico Galeazzi, Cell and Tissue Engineering Laboratory, Milan, Italy

Purpose/Objective:

Pancreatic cancer is one of the leading causes of cancer-related mortality, with a mere 10% 5-year survival rate and approximately 400,000 new cases annually [1,2]. The primary form is pancreatic ductal adenocarcinoma (PDAC). These tumors are frequently characterized by a desmoplastic environment with a dense and abundant collagenous stroma. Such a peculiar microenvironment plays an essential role in determining the outcome of different treatments, hindering drug delivery and leading to hypoxia [1,3]. Therefore, we propose an innovative in-vitro approach to replicate the peculiar microenvironment of this tumor. Based on microfluidic technology and human 3D cell culture, we aim to replicate a tumor-specific microenvironment with pancreatic-specific microvasculature. This new technology combines tumor spheroids with a vascularized microenvironment, enabling the in-vitro assessment of various treatment combinations.

Material/Methods:

The chip was designed to host two different environments within separate compartments (Figure 1). The chip was then fabricated using the typical soft-lithography method [4]. These two compartments house the tumor microenvironment and the vascular microenvironment.