Evaluation der Behandlung mit KAN0438757 in Kombination mit verschiedenen Chemotherapien im glykolytischen und lipogenen Subtyp des duktalen Pankreaskarzinoms

Evaluation of treatment with KAN0438757 in combination with different chemotherapies in the glycolytic and lipogenic subtypes of pancreatic ductal adenocarcinoma

by Anne Sophie Mittlmeier
Doctoral thesis
Date of Examination:2025-05-05
Date of issue:2025-04-14
Advisor:PD Dr. Dr. Lena-Christin Conradi
Referee:PD Dr. Dr. Lena-Christin Conradi
Referee:Prof. Dr. Elisabeth Hessmann
Persistent Address: http://dx.doi.org/10.53846/goediss-11205

 

 

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Abstract

English

Despite current treatment options, the 5-year survival rate for patients with pancreatic ductal adenocarcinoma is below 10%. This highlights the relevance of new therapeutic approaches. Pancreatic ductal adenocarcinoma, which shows metabolic dependence, can be divided into different tumor groups, of which the glycolytic subtype has a more aggressive phenotype with shorter survival. The aim of the project was to combine and evaluate the glycolytic inhibitor KAN0438757 with the chemotherapies gemcitabine, 5-FU, FOLFIRINOX, and gemcitabine + paclitaxel. Both the cell viability and colony formation assays showed that the combination treatment of all tested chemotherapies with KAN0438757 significantly reduced the viability and clonogenic capacity of the pancreatic cancer cell lines HPAF-II and MIA PaCa-2. The reduction in cell viability and clonogenic capacity was more pronounced in the more aggressive cell line MIA PaCa-2, as it belongs to the glycolytic subtype. As the influence of the combination treatment on the marker pH2AX could not be demonstrated by Western blotting, the project leaves open how the significant results of the combination of chemotherapy and KAN0438757 in the viability and colony formation assays can be explained at protein level. In summary, the data with significant effects of the combination treatment of chemotherapy with KAN0438757 show promising new therapeutic approaches for targeted treatment of ductal pancreatic carcinoma, depending on the metabolic subtype.
Keywords: pancreatic ductal adenocarcinoma