Tumor vessel normalization through inhibition of glycolysis in colorectal carcinoma

von Shuang Fan geb. Shuang Fan
Dissertation
Datum der mündl. Prüfung:2024-09-11
Erschienen:2024-09-16
Betreuer:PD Dr. Lena-Christin Conradi
Gutachter:PD Dr. Lena-Christin Conradi
Gutachter:Prof. Dr. Dieter Kube
Gutachter:Prof. Dr. Margarete Schön
Zum Verlinken/Zitieren: http://dx.doi.org/10.53846/goediss-10703

 

 

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Englisch

The current treatment approach for CRC involves a combination of surgery and neoadjuvant chemo- and RT. However, drug resistance and recurrence remain significant challenges, emphasizing the need for new and more effective treatments. Recent research has suggested that inhibiting the glycolytic activator PFKFB3 to promote TVN may improve tumor hypoxia and enhance tumor response to therapy. In this research, we performed in vivo and in vitro assays with PDOs, PDXs and CRC cells to evaluate the impact of 3PO, a PFKFB3 inhibitor on cell survival, clonogenicity, migration, invasion and metabolism. Our findings demonstrate that 3PO enhances radiation-induced CRC cell death, diminishes the metastatic and invasive abilities, and alters the transcriptional metabolism of PDOs, promoting a metabolic shift towards oxidative phosphorylation. Importantly, our results show that 3PO can induce TVN in RC, reducing the tumors’ hypoxic environment and enhancing its sensitivity to RT. Collectively, these outcomes point to the conclusion that inhibiting PFKFB3 to facilitate TVN for improve tumor hypoxia, which could represent a compelling new direction for the treatment of CRC. This research might improve to the exploitation of new therapeutic approaches for CRC patients, potentially improving their outcomes.
Keywords: Colorectal Cancer; PFKFB3 Inhibition; Tumor Vessel Normalization
 
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