ESTRO 2025 - Abstract Book

S3999

Radiobiology - Tumour radiobiology

ESTRO 2025

Results: We included a total of 9.894 NSCLC patients. Toxicity profiles were not affected when NSCLC patients were taking sertraline during any type of therapy regimens (Figure 1). Survival was not altered in the sertraline group, besides a slight disadvantage when combined with targeted therapy (p=0.046), similar to other SSRI’s. Conclusion: Considering that the sertraline and SSRI user groups might be a selected group of NSCLC patients with poorer quality of life and/or prognosis during their treatment course, main toxicities are not affected by concomitant sertraline treatment, providing evident indications for a future clinical trial to test anticancer effects in serine/glycine dependent NSCLC subgroups. References: 1. Geeraerts et al. The ins and outs of serine and glycine metabolism in cancer. Nature Met. doi: 10.1038/s42255 020-00329-9. 2. Sánchez-Castillo et al. Linking Serine/Glycine Metabolism to Radiotherapy Resistance. Cancers 10;13(6):1191. 3. Heylen et al. Transcription factor NKX2-1 drives serine and glycine addiction in cancer. Br J Cancer. doi: 10.1038/s41416-023-02216-y. 4. Kampen et al. Repurposing the antidepressant sertraline as SHMT inhibitor to suppress serine/glycine synthesis addicted breast tumor growth. Mol Cancer Ther 20 (1) 50-63. 5. Sánchez-Castillo et al. Targeting serine/glycine metabolism improves radiotherapy responses in Non-Small Cell Lung Cancer. Br J Cancer. 130(4):568-584. doi: 10.1038/s41416-023-02553-y. Keywords: sertraline, retrospective study, NSCLC Digital Poster MitoTam as OXPHOS inhibitor: reducing hypoxia in solid tumors Anne P.M. Beerkens 1 , Gosse J. Adema 1 , Sandra Heskamp 2 , Paul N. Span 1 , Johan Bussink 1 1 Radiation Oncology, Radboud University Medical Center, Nijmegen, Netherlands. 2 Medical Imaging, Radboud University Medical Center, Nijmegen, Netherlands Purpose/Objective: An imbalance between oxygen consumption and oxygen supply causes hypoxia in solid tumors. Tumor hypoxia is associated with an aggressive phenotype and poor response to anti-cancer therapies. To achieve a durable reduction of hypoxia, it is proposed to decrease oxygen consumption in tumor tissue and thereby reduce hypoxia. We aim to reduce tumor hypoxia through inhibition of OXPHOS using the mitochondria-targeted triphenylphosphonium (TPP+) conjugated OXPHOS inhibitors MitoTam and Mito-PEG-ATO. These mito-targeted inhibitors preferentially target mitochondria of cancerous cells, resulting in increased tumor cell uptake compared with healthy cells, thereby increasing the therapeutic window. Material/Methods: Mice were inoculated with MOC1.3D5 tumor cells on the right hindleg. When tumors reached an average size of approximately 80 mm3, mice were treated with Mito-PEG-ATO (20 mg/kg) for 10 consecutive days. To mark hypoxia, proliferation and perfusion, mice were injected with pimonidazole and BrdUrd 1h prior to sacrifice and Hoechst 1 min prior to sacrifice, respectively. Blood was drawn to perform lactate measurements on serum. Spheroids were grown from murine melanoma (B16OVA) and colon cancer (MC38) cells containing a HIF1-α responsive element (HRE)-eGFP construct. 24h after spheroid formation, treatment was started with MitoTam 0.625, 1.25, 2.5 and 5 µM. Diffusion-limited hypoxia was quantified using a Live-cell imaging system. 2606