More than half of all cancer patients are treated with radiotherapy. To increase the clinical benefit of radiotherapy, the treatment is often combined with chemotherapy and/or immunotherapy. Optimizing such combination therapies requires insight in the responses that occur in cancer cells during radiotherapy. To identify key responses, Victor Thijssen (department of Radiation Oncology, Amsterdam UMC) and colleagues monitored the molecular changes during fractionated irradiation in different types of cancer cells and in a mouse tumor model. They identified the type I interferon response as a key response to treatment. Activation of this response during chemoradiotherapy was confirmed in tumor tissues from esophageal cancer patients. Importantly, the researchers found that blocking the signaling pathway that triggers the interferon response, the cGAS/STING pathway, could delay but not prevent the response. This has implications for current efforts that aim to target cGAS/STING signaling because the findings indicate that alternative signaling pathways can provide an escape mechanism to treatment. The current research of the group aims to identify the proteins that are involved in this escape mechanisms and the therapeutic opportunities to target these proteins. This will help to improve the efficacy of radiotherapy.
Download the full article
People involved:
Ruben Goedegebuure, Amsterdam UMC
Esther Kleibeuker, Amsterdam UMC
Francesca Buffa, Oxford University
Kitty Castricum, Amsterdam UMC
Syed Haider, Oxford University
Iris Schulkens, Amsterdam UMC
Luuk ten Kroode, Amsterdam UMC
Jaap van den Berg, Amsterdam UMC
Maarten Jacobs, Amsterdam UMC
Anne-Marie van Berkel, Noord West Ziekenhuisgroep
Nicole van Grieken, Amsterdam UMC
Sarah Derks, Amsterdam UMC
Ben Slotman, Amsterdam UMC
Henk Verheul, Radboud UMC
Adrian Harris, Oxford University
Victor Thijssen, Amsterdam UMC