New therapeutic approach to pancreatic cancer
A research team at Magdeburg University Hospital discovers a promising combination of active substances
Pancreatic cancer is one of the most aggressive cancers with a very poor prognosis. One of the main reasons for this is the ability of tumour cells to evade programmed cell death (apoptosis). A research team from the Faculty of Medicine at Otto von Guericke University Magdeburg has now developed a new substance that specifically interferes with this mechanism and could improve the effectiveness of existing cancer therapies. The results of the current study have been published in the journal Communications Biology.
Apoptosis is an essential biological process that controls both the development of healthy organisms and the elimination of damaged or abnormal cells. Dysregulation of this mechanism can contribute to the development of numerous diseases, including cancer. ‘All diseases in our body are associated with a dysregulation of apoptosis. In order to develop new, specific therapies, it is important to develop substances that either inhibit or promote apoptosis,’ explains Prof. Dr habil. Inna Lavrik, head of the Translational Inflammation Research Group at the University of Magdeburg.
_Fotograf privat.jpg "Autorenteam um Prof. Inna Lavrik (2.v.l.)_Fotograf privat")
Photo (private): Authors of the manuscript of the WG TEF (from left): M Dr rer. nat. Nikita Ivanisenko, Prof. Dr habil. Inna Lavrik, M. Sc. Corinna König
New drug combination increases tumour cell death
In order to specifically intervene in the apoptosis mechanism, the research team combined computer-based methods with experimental analyses. The study focussed on the protein c-FLIPL, an important regulator of apoptosis. The research team developed the drug FLIPinB, which specifically binds to this protein and thus triggers an important process: it activates the enzyme caspase-8, which triggers cell death in cancer cells. This targeted influence reactivates the natural mechanism of apoptosis, which tumour cells often bypass in order to continue growing uncontrollably.
In the current study, FLIPinB was also combined with two other drugs that are already used in the treatment of pancreatic cancer: the chemotherapeutic agent gemcitabine and the Mcl-1 inhibitor S63845. The results show that this combination of active substances increases the formation of a crucial protein complex - complex II - which triggers cell death in tumour cells. In laboratory experiments, this targeted treatment led to a significant reduction in tumour cells, while healthy cells remained largely unaffected.
‘Our results show that we can open up new therapeutic avenues for pancreatic cancer by targeting apoptosis regulators. The combination of FLIPinB, gemcitabine and Mcl-1 inhibitors could significantly improve the efficacy of treatment while reducing side effects,’ summarises Prof. Lavrik.
The findings from this study provide a promising basis for further preclinical and clinical investigations. In the long term, this strategy could contribute to the development of more effective and better tolerated therapies for pancreatic cancer.
Translational Inflammation Research Group
The research work of the Translational Inflammation Research Group at the University Medical Centre Magdeburg is characterised by its interdisciplinary approach. Researchers from the fields of apoptosis, inflammation research, structural biology, pharmacology and systems biology work together on innovative approaches to fighting cancer. In close cooperation with other faculties of the University of Magdeburg and the Max Planck Institute at the Research Center Dynamic Systems - Biosystems Engineering (CDS), they are using mathematical modelling and experimental medicine to develop new therapeutic strategies.
The research is funded by the European Regional Development Fund (ERDF).
Original publication
König C, Ivanisenko NV, Ivanisenko VA, Kulms D, Lavrik IN. Pharmacological targeting of caspase-8/c-FLIPL heterodimer enhances complex II assembly and elimination of pancreatic cancer cells. Commun Biol. 2025 Jan 3;8(1):4. doi: 10.1038/s42003-024-07409-6. PMID: 39753884; PMCID: PMC11698904.
Scientific Contact
Prof. Dr. Inna Lavrik, Head of the Translational Inflammation Research Group, Dynamic Systems Research Centre (CDS), Medical Faculty of Otto von Guericke University Magdeburg, Phone: +49 391 67-54767, Inna.lavrik@med.ovgu.de
New drug combination increases tumour cell death