Targeting Glutamatergic Signaling and the PI3 Kinase Pathway to Halt Melanoma Progression

Translational Oncology
Stephen A RosenbergJames S Goydos

Abstract

Our group has previously reported that the majority of human melanomas (>60%) express the metabotropic glutamate receptor 1 (GRM1) and that the glutamate release inhibitor riluzole, a drug currently used to treat amyotrophic lateral sclerosis, can induce apoptosis in GRM1-expressing melanoma cells. Our group previously reported that in vitro riluzole treatment reduces cell growth in three-dimensional (3D) soft agar colony assays by 80% in cells with wildtype phosphoinositide 3-kinase (PI3K) pathway activation. However, melanoma cell lines harboring constitutive activating mutations of the PI3K pathway (PTEN and NRAS mutations) showed only a 35% to 40% decrease in colony formation in soft agar in the presence of riluzole. In this study, we have continued our preclinical studies of riluzole and its effect on melanoma cells alone and in combination with inhibitors of the PI3 kinase pathway: the AKT inhibitor, API-2, and the mammalian target of rapamycin (mTOR) inhibitor, rapamycin. We modeled these combinatorial therapies on various melanoma cell lines in 3D and 2D systems and in vivo. Riluzole combined with mTOR inhibition is more effective at halting melanoma anchorage-independent growth and xenograft tumor progression than eith...Continue Reading

References

Jan 1, 1997·Annual Review of Pharmacology and Toxicology·P J Conn, J P Pin
Oct 6, 2000·The American Journal of Pathology·X P ZhouC Eng
Aug 16, 2001·Proceedings of the National Academy of Sciences of the United States of America·M S NeshatC L Sawyers
Jun 1, 2002·Science·Lewis C Cantley
Jul 3, 2002·Nature Reviews. Cancer·Igor Vivanco, Charles L Sawyers
Jun 23, 2005·Frontiers in Bioscience : a Journal and Virtual Library·Friedegund MeierMeenhard Herlyn
Jul 26, 2005·Neuropharmacology·Yarí E MarínSuzie Chen
Oct 19, 2005·Proceedings of the National Academy of Sciences of the United States of America·Andrzej StepulakChrysanthy Ikonomidou
Nov 18, 2005·The New England Journal of Medicine·John A CurtinBoris C Bastian
Dec 17, 2005·Current Opinion in Oncology·Yardena Samuels, Kajsa Ericson
Jul 5, 2006·Cancer Research·Alireza MirmohammadsadeghUlrich R Hengge
Mar 3, 2007·Cancer Research·Jin NamkoongSuzie Chen
Mar 21, 2007·Pigment Cell Research·Tanja Rothhammer, Anja-Katrin Bosserhoff
Jul 3, 2007·Cell·Brendan D Manning, Lewis C Cantley
Oct 5, 2007·The Journal of Investigative Dermatology·Magdalena KarbowniczekElizabeth P Henske
Jan 4, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nikolas K HaassKeiran S M Smalley
Jun 17, 2008·Neuropharmacology·Seung-Shick ShinSuzie Chen
Aug 6, 2008·Molecular Pharmaceutics·Jayme L HorningVinod Labhasetwar
Sep 4, 2008·Current Oncology Reports·Keith T Flaherty
Sep 17, 2008·Oncogene·T L Yuan, L C Cantley
May 22, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Dana YipJames S Goydos
Sep 29, 2009·Critical Reviews in Oncology/hematology·Roger MouawadDavid Khayat
Oct 22, 2009·Pigment Cell & Melanoma Research·Seung-Shick ShinSuzie Chen
Feb 4, 2010·Expert Review of Dermatology·Papia Ghosh, Lynda Chin
May 28, 2010·The Journal of Investigative Dermatology·Maithao N LeJames S Goydos
Jun 8, 2010·The New England Journal of Medicine·F Stephen HodiWalter J Urba
Nov 5, 2010·The Journal of Investigative Dermatology·Johannes WerzowaVolker Wacheck
Dec 21, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Saadia A AzizHarriet M Kluger
Jun 7, 2011·The New England Journal of Medicine·Paul B ChapmanUNKNOWN BRIM-3 Study Group
Oct 2, 2012·The New England Journal of Medicine·Keith T FlahertyJeffrey Weber
Dec 18, 2013·Pigment Cell & Melanoma Research·Brian A WallSuzie Chen

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Citations

Sep 10, 2015·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yan JiangChang Liu
May 6, 2016·Breast Cancer Research and Treatment·Cecilia L SpeyerDavid H Gorski
Jun 6, 2018·Macromolecular Rapid Communications·Zheng LuoYun-Long Wu
Dec 13, 2017·Oncotarget·Swetlana SperlingMilena Ninkovic
Oct 21, 2017·Cell Communication and Signaling : CCS·Simar J SinghFabian V Filipp
Aug 7, 2017·Breast Cancer Research and Treatment·Cecilia L SpeyerDavid H Gorski
Mar 1, 2016·Melanoma Management·Russell W Jenkins, Ryan J Sullivan
Aug 8, 2020·Frontiers in Cell and Developmental Biology·Qifu XuYingjie Zhang
Jun 18, 2015·Molecular Cancer Research : MCR·Gregory R KardosGavin P Robertson
Nov 6, 2020·European Journal of Medicinal Chemistry·Yichao WanZilong Tang
Aug 8, 2021·Cancers·Kevinn Eddy, Suzie Chen
Oct 31, 2021·Experimental Dermatology·Gennie L ParkmanMartin McMahon

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Methods Mentioned

BETA
X-ray
xenograft
xenografts

Software Mentioned

Gene Tools
Syngene

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