Tamoxifen is a candidate first-in-class inhibitor of acid ceramidase that reduces amitotic division in polyploid giant cancer cells-Unrecognized players in tumorigenesis

Cancer Medicine
Shai White-GilbertsonChristina Voelkel-Johnson

Abstract

Polyploid giant cancer cells (PGCC) represent a poorly understood, small subpopulation of tumor cells that are increasingly being recognized for their critical role in therapy resistance, metastasis, and cancer recurrence. PGCC have the potential to generate progeny through primitive or cleavage-like division, which allows them to evade antimitotic insults. We recently demonstrated that the sphingolipid enzyme acid ceramidase (ASAH1) is required for this process. Since specific ASAH1 inhibitors are not clinically available, we investigated whether tamoxifen, which interferes with ASAH1 function via off-target effects, has a potential clinical benefit independent of estrogen signaling. Our results show that tamoxifen inhibits generation of PGCC offspring in prostate cancer, glioblastoma, and melanoma cells. Analysis of two state-level cancer registries revealed that tamoxifen improves survival outcomes for second, nonbreast cancers that develop in women with early stage breast cancer. Our results suggest that tamoxifen may have a clinical benefit in a variety of cancers that is independent of estrogen signaling and could be due to its inhibition of acid ceramidase. Thus the distinct application of tamoxifen as potentially a firs...Continue Reading

References

Mar 15, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·A BroniscerL M Cristófani
Aug 31, 2000·Cell Biology International·T M IllidgeJ A Erenpreisa
Apr 10, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Elton R KisangaErnst A Lien
Dec 1, 2005·Cell Biology International·Rengaswami RajaramanDuane L Guernsey
Feb 1, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Efrat EliyahuEdward H Schuchman
Oct 5, 2010·International Journal of Dermatology·Julieta Ruiz BeguerieRaúl P Valdez
Jan 26, 2011·Cancer·Christine BouchardyElisabetta Rapiti
Apr 16, 2011·The Journal of Biological Chemistry·Natasha C Lucki, Marion B Sewer
Aug 3, 2012·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Efrat EliyahuEdward H Schuchman
Aug 14, 2013·Biochimica Et Biophysica Acta·Samy A F MoradMyles C Cabot
Oct 5, 2013·The Journal of Clinical Investigation·Joseph C ChengXiang Liu
Jun 7, 2014·Frontiers in Oncology·Jermaine Coward, Angus Harding
May 13, 2015·Biochimica Et Biophysica Acta·Samy A F Morad, Myles C Cabot
Nov 4, 2017·Journal of Cancer Research and Clinical Oncology·Holm EggemannAtanas Ignatov
Jun 27, 2018·The American Journal of Surgical Pathology·Abdullah M AlharbiJonathan I Epstein
Aug 1, 2018·Advances in Cancer Research·Christina Voelkel-JohnsonShai White-Gilbertson
Apr 17, 2019·Journal of Lipid Research·Shai White-GilbertsonChristina Voelkel-Johnson
Aug 6, 2019·Cancer·Thomas C TuckerBin Huang

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Citations

Dec 29, 2020·Seminars in Cancer Biology·Tareq SalehDavid A Gewirtz
Jan 23, 2021·RSC Medicinal Chemistry·Brandon T MillikenRobert P Doyle
Mar 18, 2021·Seminars in Cancer Biology·Halina WasClaudine Kieda
Apr 12, 2021·Seminars in Cancer Biology·Jing ZhangXinzhe Liu
Aug 7, 2021·Medicina·Ana Gomez-LarrauriAlberto Ouro
Dec 29, 2020·Current Cancer Drug Targets·Helen Shiphrah VethakanrajAshok Kumar Sekar

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