Metmorfin as adjuvant therapy for glioblastoma - a pathway to clinical phase I/II-trials

• Applicants: Professor Dr. Michael Leitzmann; Dr. Corinna Seliger
• Subject Area: Hematology, Oncology
• Term: from 2014 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 190230491

• Final Report Year: 2019

Final Report Abstract

Use of metformin is not associated with a reduced risk of glioma, but patients with specific glioma subtypes (i.e. WHO grade III glioma, possibly IDH-mutated gliomas, patients with a proneural signature) may be more responsive to treatment with metformin. Adding rationale combination partners may augment inhibitory effects of metformin on glioma. Future clinical trials should consider subtype specific responses and combinatorial approaches.

Publications

• (2014) Response predictive gene expression profiling of glioma progenitor cells in vitro. PLoS One Sep 30;9(9):e108632
  Moeckel S, Meyer K, Leukel P, Heudorfer F, Seliger C, Stangl C, et al.
  (See online at https://doi.org/10.1371/journal.pone.0108632)
• (2015) Ibuprofen and Diclofenac Restrict Migration and Proliferation of Human Glioma Cells by Distinct Molecular Mechanisms. PLoS One Oct 20;10(10):e0140613
  Leidgens V, Seliger C, Jachnik B, Welz T, Leukel P, Vollmann-Zwerenz A, et al.
  (See online at https://doi.org/10.1371/journal.pone.0140613)
• (2016) Diabetes, use of antidiabetic drugs, and the risk of glioma. Neuro Oncol Mar;18(3):340-9
  Seliger C, Ricci C, Meier CR, Bodmer M, Jick SS, Bogdahn U and Leitzmann MF
  (See online at https://doi.org/10.1093/neuonc/nov100)
• (2016) Metformin inhibits proliferation and migration of glioblastoma cells independently of TGF-β2. Cell Cycle Jul 2;15(13):1755-66
  Seliger C, Meyer AL, Renner K, Leidgens V, Moeckel S, Jachnik B, et al.
  (See online at https://doi.org/10.1080/15384101.2016.1186316)
• (2016) Use of cardiac glycosides and risk of glioma. J Neurooncol Apr;127(2):321-8
  Seliger C, Meier CR, Jick SS, Uhl M, Bogdahn U, Hau P and Leitzmann MF
  (See online at https://doi.org/10.1007/s11060-015-2036-2)
• (2016) Use of Selective Cyclooxygenase-2 Inhibitors, Other Analgesics, and Risk of Glioma. PLoS One Feb 12;11(2):e0149293
  Seliger C, Meier CR, Becker C, Jick SS, Bogdahn U, Hau P and Leitzmann MF
  (See online at https://doi.org/10.1371/journal.pone.0149293)
• (2016). Statin use and risk of glioma - population-based case-control analysis. Eur J Epidemiology Sep;31(9):947-52
  Seliger C, Meier CR, Becker C, Bogdahn U, Hau P and Leitzmann MF
  (See online at https://doi.org/10.1007/s10654-016-0145-7)
• (2017). Diabetes, use of metformin, and the risk of meningioma. PLoS One Jul 14;12(7): e0181089
  Seliger C, Meier CR, Becker C, Jick SS, Proescholdt M, Bogdahn U, Hau P and Leitzmann MF
  (See online at https://doi.org/10.1371/journal.pone.0181089)
• (2017). Metabolic syndrome in relation to risk of meningioma. Oncotarget Jan 10;8(2):2284-2292
  Seliger C, Meier C, Becker C, Jick S, Proescholdt M, Bogdahn U, Hau P and Leitzmann MF
  (See online at https://doi.org/10.18632/oncotarget.13667)
• (2017). Stattic and metformin inhibit brain tumor initiating cells by reducing STAT3-phosphorylation. Oncotarget Jan 31;8(5):8250-8263
  Leidgens V, Proske J, Rauer L, Moeckel S, Renner K, Bogdahn U, Riemenschneider JM, Proescholdt M, Vollmann-Zwerenz A, Hau P and Seliger C
  (See online at https://doi.org/10.18632/oncotarget.14159)
• (2018) Combined Modulation of Tumor Metabolism by Metformin and Diclofenac in Glioma. Int J Mol Sci Aug 31;19(9): pii: E2586
  Gerthofer V, Kreutz M, Renner K, Jachnik B, Dettmer K, Oefner P, Riemenschneider MJ, Proescholdt M, Vollmann-Zwerenz A, Hau P and Seliger C
  (See online at https://doi.org/10.3390/ijms19092586)
• (2018) Use of metformin and survival of patients with high-grade glioma. Int J Cancer
  Seliger C, Luber C, Gerken M, Schaertl J, Proescholdt M, Riemenschneider MJ, Meier CR, Bogdahn U, Leitzmann MF, Klinkhammer-Schalke M and Hau P
  (See online at https://doi.org/10.1002/ijc.31783)
• (2018) Use of statins or NSAIDs and survival of patients with high-grade glioma. PLoS One Dec 3;13(12): e0207858
  Seliger C, Schaertl J, Gerken M, Luber C, Proescholdt M, Riemenschneider MJ, Leitzmann MF, Hau P, Klinkhammer-Schalke M
  (See online at https://doi.org/10.1371/journal.pone.0207858)