Prof. Dr. Ian Frew

Our research lies at the interface of basic and translational cancer research. We ask how different combinations of genetic mutations in tumour suppressor and oncogenic signalling pathways affect the behaviours of tumours and their responses to therapies. We employ a variety of genetic approaches to tackle these questions, with current major research interests in kidney tumours and different types of sarcomas. In addition to the use of conventional mouse genetics, we develop new tools that allow more rapid genetic approaches in mice with the aim of being able to more efficiently and rapidly investigate the combined effects of genetic alterations in multiple signalling pathways and biological processes. We utilise both genetic and chemical library screening approaches to identify therapeutic sensitivities based on the mutational spectrum of tumours and conduct pre-clinical tests of molecularly-targeted agents using our mouse models. We also aim to work closely with oncologists and pathologists to translate these findings to the clinic.

10 selected publications

• ATR represents a therapeutic vulnerability in clear cell renal cell carcinoma.
  Seidel P, Rubarth A, Zodel K, Peighambari A, Neumann F, Federkiel Y, Huang H, Hoefflin R, Adlesic M, Witt C, Hoffmann DJ, Metzger P, Lindemann RK, Zenke FT, Schell C, Boerries M, von Elverfeldt D, Reichardt W, Follo M, Albers J, Frew IJ.
  JCI Insight. 2022 Dec 22;7(24):e156087.
• Therapeutic Effects of Inhibition of Sphingosine-1-Phosphate Signaling in HIF-2α Inhibitor-Resistant Clear Cell Renal Cell Carcinoma.
  Hoefflin R, Harlander S, Abhari BA, Peighambari A, Adlesic M, Seidel P, Zodel K, Haug S, Göcmen B, Li Y, Lahrmann B, Grabe N, Heide D, Boerries M, Köttgen A, Heikenwalder M, Frew IJ.Cancers (Basel).
  2021 Sep 25;13(19):4801.
• HIF-1α and HIF-2α differently regulate tumour development and inflammation of clear cell renal cell carcinoma in mice.
  Hoefflin R, Harlander S, Schäfer S, Metzger P, Kuo F, Schönenberger D, Adlesic M, Peighambari A, Seidel P, Chen CY, Consenza-Contreras M, Jud A, Lahrmann B, Grabe N, Heide D, Uhl FM, Chan TA, Duyster J, Zeiser R, Schell C, Heikenwalder M, Schilling O, Hakimi AA, Boerries M, Frew IJ.
  Nat Commun. 2020 Aug 17;11(1):4111.
• Evidence of renal angiomyolipoma neoplastic stem cells arising from renal epithelial cells.
  Filipa Gonçalves A, Adlesic M, Brandt S, Hejhal T, Harlander S, Sommer L, Shakhova O, Wild PJ, Frew IJ.
  Nat Commun. 2017 Nov 13;8(1):1466.
• Combined mutation in Vhl, Trp53 and Rb1 causes clear cell renal cell carcinoma in mice.
  Harlander S, Schönenberger D, Toussaint NC, Prummer M, Catalano A, Brandt L, Moch H, Wild PJ, Frew IJ.
  Nat Med. 2017. 23: 869-877.
• Combined deletion of Vhl, Trp53 and Kif3a causes cystic and neoplastic renal lesions.
  Guinot A, Lehmann H, Wild PJ, Frew IJ.
  J Pathol. 2016 Jul;239(3):365-73.
• Formation of renal cysts and tumors in Vhl/Trp53-deficient mice requires HIF1α and HIF2α.
  Schönenberger D, Harlander S, Rajski M, Jacobs RA, Lundby AK, Adlesic M, Hejhal T, Wild PJ, Lundby C, Frew IJ.
  Cancer Res. 2016 Apr 1;76(7):2025-36.
• A versatile modular vector system for rapid combinatorial mammalian genetics.
  Albers J, Danzer C, Rechsteiner M, Lehmann H, Brandt LP, Hejhal T, Catalano A, Busenhart P, Gonçalves AF, Brandt S, Bode PK, Bode-Lesniewska B, Wild PJ, Frew IJ.
  J Clin Invest. 2015 Apr;125(4):1603-19.
• Combined deletion of Vhl and Kif3a accelerates renal cyst formation.
  Lehmann H, Vicari D, Wild PJ, Frew IJ.
  J Am Soc Nephrol. 2015 Nov;26(11):2778-88.
• Combined mutation of Vhl and Trp53 causes renal cysts and tumours in mice.
  Albers J, Rajski M, Schönenberger D, Harlander S, Schraml P, von Teichman A, Georgiev S, Wild PJ, Moch H, Krek W, Frew IJ.
  EMBO Mol Med. 2013 Jun;5(6):949-64.

See all publications (PubMed link)