Protect – proton versus photon therapy for esophageal Cancer

Principal Investigators: prof. dr. Mischa Hoogeman (HollandPTC and dr Hedwig Blommestein (HollandPTC)

 PhD students: Quais Akolawala (TU Delft)

Funding: TU Delft Health Initiative 2022

Description

The development of physiological engineered in vitro models assumes a pivotal role in the understanding and treatment of diseases. Among these, glioblastoma is the most aggressive type of brain cancer with a yearly incidence of 3 cases per 100,000 people. Prospects for patients are bleak, with a median survival of just 15 months after diagnosis despite chemoand radiotherapy. An alternative promising solution is proton therapy, which is able to offer effective treatment with less radiation exposure to the brain. In particular, FLASH proton therapy, compared to conventional dose-rate irradiation, is 400-fold more rapid (≥ 40 Gy/s), thus further reducing the damage to healthy tissue and shortening treatment time. However, systematic in vivo studies of the effect of FLASH proton therapy on glioblastoma are lacking, as are reliable in vitro platforms to assess dose efficiency. This is because investigations on the morphological and functional changes of cells after being exposed, cannot be routinely performed on patients or tissues coming from biopsies. On the other hand, in vitro studies of cells mostly rely on strategies that do not realistically represent the three-dimensional (3D) spatial configuration in our brain.

There is therefore an urgent need for 3D cell-instructive microenvironments that can be (1) exploited as standardized and biomimetic in vitro models for understanding how the third dimension affects brain cancer cell development, and (2) used as a platform to assess FLASH therapy. The development of reliable 3D organ-on-chip devices is of central interest for the Netherlands’ Top Sector “Life Science and Health”. Current approaches include, however, either 3D microenvironments or microfluidic devices; a platform embedding both features is still missing. To fill this gap, we propose to realize a standardized, reproducible, and physiologically relevant 3D glioblastoma organ-on-chip and use it for assessing the effect of FLASH protontherapy.