Name: Katrien Konings
Date: February 22, 2019 15:00h
Auditorium Oude Molen
Kasteelpark Arenberg 50
Impact of different radiation qualities on molecular and functional changes in cancer cells: role of Hedgehog signaling?
Currently, an increasing number of cancer patients is being treated with particle therapy. Although the physical properties are well characterized, many questions related to the biological effects of particles remain. Therefore it is of utmost importance to further increase our knowledge on the molecular and cellular effects of particle radiation since these can be different from conventional X-rays.
In this PhD project, the biological effects of conventional X-rays, protons and carbon ions were compared in different human cancer cell lines. In addition, we focused on the Hedgehog (Hh) signaling pathway because evidence has shown that activation of this pathway is linked to the development and the progression of several different tumor types. Furthermore, an active Hh pathway has been associated with resistance to conventional radiotherapy and X-irradiation has been shown to activate the Hh pathway. Therefore, the main goal was to study the impact of Hh pathway inhibition in combination with radiation exposure on several biological and functional endpoints. More specifically, we investigated the effect of particle radiation at both (1) molecular (DNA damage, cell cycle, Hh pathway gene expression) and (2) cellular (cell survival and migration) levels. In conclusion, we demonstrated that carbon ions were more effective than X-rays in delaying DNA damage repair, inducing cell cycle arrest, decreasing cell survival, decreasing migration and more significantly altering the Hh pathway gene expression. Moreover, while the calculated RBE10 for protons was around 1, differences in migration potential and changes of the Hh pathway gene expression was observed in cancer cells compared to X-ray irradiation. In addition, Hedgehog inhibitor GANT61 was able to sensitize medulloblastoma cells to particle radiation (protons and carbon ions) but not to X-rays. To conclude, our data show the potential of particle therapy and underline the fact that molecular targeted drugs might be promising in combination with particle therapy.
- (KULeuven) Karin Haustermans
- Marjan Moreels
- Sarah Baatout
Click here for a list of obtained PhD degrees.