EGF Receptor and mTORC1 Are Novel Therapeutic Targets in Nonseminomatous Germ Cell Tumors

Molecular Cancer Therapeutics
Kenneth S ChenJames Amatruda

Abstract

Germ cell tumors (GCT) are malignant tumors that arise from pluripotent embryonic germ cells and occur in children and young adults. GCTs are treated with cisplatin-based regimens which, while overall effective, fail to cure all patients and cause significant adverse late effects. The seminoma and nonseminoma forms of GCT exhibit distinct differentiation states, clinical behavior, and response to treatment; however, the molecular mechanisms of GCT differentiation are not fully understood. We tested whether the activity of the mTORC1 and MAPK pathways were differentially active in the two classes of GCT. Here we show that nonseminomatous germ cell tumors (NSGCT, including embryonal carcinoma, yolk sac tumor, and choriocarcinoma) from both children and adults display activation of the mTORC1 pathway, while seminomas do not. In seminomas, high levels of REDD1 may negatively regulate mTORC1 activity. In NSGCTs, on the other hand, EGF and FGF2 ligands can stimulate mTORC1 and MAPK signaling, and members of the EGF and FGF receptor families are more highly expressed. Finally, proliferation of NSGCT cells in vitro and in vivo is significantly inhibited by combined treatment with the clinically available agents erlotinib and rapamycin,...Continue Reading

References

Apr 17, 1999·Journal of Pediatric Hematology/oncology·G A HaleM M Hudson
Jul 4, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M HidalgoE K Rowinsky
Apr 30, 2002·Genes, Chromosomes & Cancer·Sigrid Marie KraggerudRagnhild A Lothe
Aug 15, 2002·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J T HartmannC Bokemeyer
Jan 2, 2003·Nature Reviews. Cancer·J Wolter OosterhuisEvert-Ben van Veen
May 20, 2004·British Journal of Cancer·E A RapleyM R Stratton
Sep 24, 2004·International Journal of Cancer. Journal International Du Cancer·Florian SommererAndrea Tannapfel
Mar 2, 2005·Nature Reviews. Cancer·J Wolter Oosterhuis, Leendert H J Looijenga
Dec 16, 2005·Neoplasia : an International Journal for Oncology Research·Alan McIntyreJanet Shipley
Jul 11, 2006·Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society·Michael K FritschElizabeth J Perlman
Dec 21, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Martine L M LamfersClemens M F Dirven
Jun 4, 2008·Cancer Research·Roger D PalmerUNKNOWN Children's Cancer and Leukaemia Group
Oct 31, 2008·Melanoma Research·Pierre L TriozziChristopher Dombos
May 7, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wilmar Castillo-AvilaFrancesc Viñals
Jun 2, 2009·Nature Genetics·Elizabeth A RapleyMichael R Stratton
Jun 2, 2009·Nature Genetics·Peter A KanetskyKatherine L Nathanson
Mar 25, 2010·The Oncologist·Virginia E KwitkowskiRichard Pazdur
Jul 7, 2010·Cell·Mark A Lemmon, Joseph Schlessinger
Aug 10, 2010·Cell·Robin M HobbsPier Paolo Pandolfi
Sep 3, 2010·The Journal of Clinical Investigation·Roelof KosterSteven de Jong
Dec 24, 2010·Molecular Systems Biology·Etienne CaronHiroaki Kitano
Feb 18, 2011·Endocrinology·Paul LanglaisLawrence J Mandarino
Jul 22, 2011·Proceedings of the National Academy of Sciences of the United States of America·Joanie C NeumannJames F Amatruda
Nov 2, 2011·Journal of Receptor and Signal Transduction Research·Mouna Choura, Ahmed Rebaï
Nov 11, 2011·Genes, Chromosomes & Cancer·Jenny N PoynterJulie A Ross
Jun 8, 2012·Science Translational Medicine·Sharanya SivanandJames Brugarolas
Jan 8, 2013·International Journal of Cancer. Journal International Du Cancer·M JuliachsF Viñals
Aug 21, 2013·Pediatric Blood & Cancer·Daniel A MorgensternSylvain Baruchel
Nov 28, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·M JuliachsF Viñals
Jan 24, 2014·Acta Neuropathologica·Shintaro FukushimaUNKNOWN Intracranial Germ Cell Tumor Genome Analysis Consortium (iGCT Consortium)
May 9, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Darren R FeldmanDavid B Solit

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