Genetic Instability and Resistance

Exploiting the IGF pathway for the treatment of Osteosarcoma and brain tumors

The insulin-like growth factor (IGF) pathway has long been recognised as a major molecular target in pediatric tumors. However, clinical studies of IGF-1 receptor (IGF-1R)-targeted monotherapies have been largely disappointing and no inhibitors have been released to date. Our hypothesis is that the crosstalk between the IGF pathway and other tyrosine kinases receptors (RTKs) can influence the efficacy of the IGF inhibition. We are therefore interested in the identification of interaction partners of IGF1-R, particularly in osteosarcoma (OS) and brain tumors. As functional model we are using primary tumor cells of OS patients. The cells are used for a pharmacological screening with IGF inhibitors to identify the best drug combination at the individual level.

Contact:  Dr. rer. nat. Claudia Paret, PD Dr. med. Alexandra Russo and Dr. med. Oaf Beck

Project relevant Publications:

Beck O, Paret C, Russo A, Burhenne J, Fresnais M, Steimel K, Seidmann L, Wagner DC, Vewinger N, Lehmann N, Sprang M, Backes N, Roth L, Neu MA, Wingerter A, Henninger N, Malki KE, Otto H, Alt F, Desuki A, Kindler T, Faber J. Safety and Activity of the Combination of Ceritinib and Dasatinib in Osteosarcoma. Cancers (Basel). 2020 Mar 26;12(4):793. doi: 10.3390/cancers12040793. PMID: 32224911; PMCID: PMC7225940.

Russo A, Paret C, Alt F, Burhenne J, Fresnais M, Wagner W, Glaser M, Bender H, Huprich S, Harter PN, Filipski K, Lehmann N, Backes N, Roth L, Seidmann L, Sommer C, Brockmann MA, Pietsch T, Neu MA, Wingerter A, Faber J. Ceritinib-Induced Regression of an Insulin-Like Growth Factor-Driven Neuroepithelial Brain Tumor. Int J Mol Sci. 2019 Aug 30;20(17):4267. doi: 10.3390/ijms20174267. PMID: 31480400; PMCID: PMC6747232.

Vewinger N, Huprich S, Seidmann L, Russo A, Alt F, Bender H, Sommer C, Samuel D, Lehmann N, Backes N, Roth L, Harter PN, Filipski K, Faber J, Paret C. IGF1R Is a Potential New Therapeutic Target for HGNET-BCOR Brain Tumor Patients. Int J Mol Sci. 2019 Jun 21;20(12):3027. doi: 10.3390/ijms20123027. PMID: 31234291; PMCID: PMC6627083.