Sunitinib induces early histomolecular changes in a subset of renal cancer cells that contribute to resistance

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Zsuzsanna LichnerGeorge M Yousef

Abstract

Sunitinib is the standard-of-care, first-line treatment for advanced renal cell carcinoma (RCC). Characteristics of treatment-resistant RCC have been described; however, complex tumor adaptation mechanisms obstruct the identification of significant operators in resistance. We hypothesized that resistance is a late manifestation of early, treatment-induced histomolecular alterations; therefore, studying early drug response may identify drivers of resistance. We describe an epithelioid RCC growth pattern in RCC xenografts, which emerges in sunitinib-sensitive tumors and is augmented during resistance. This growth modality is molecularly and morphologically related to the RCC spheroids that advance during in vitro treatment. Based on time-lapse microscopy, mRNA and microRNA screening, and tumor behavior-related characteristics, we propose that the spheroid and adherent RCC growth patterns differentially respond to sunitinib. Gene expression analysis indicated that sunitinib promoted spheroid formation, which provided a selective survival advantage under treatment. Functional studies confirm that E-cadherin is a key contributor to the survival of RCC cells under sunitinib treatment. In summary, we suggest that sunitinib-resistant R...Continue Reading

References

Dec 6, 2001·Nature Reviews. Molecular Cell Biology·M Fukata, K Kaibuchi
Jun 1, 2002·Science·Susana R NevesRavi Iyengar
Jan 12, 2007·The New England Journal of Medicine·Robert J MotzerRobert A Figlin
Jul 28, 2007·Nature Clinical Practice. Oncology·James M G LarkinMartin E Gore
Jan 9, 2009·PLoS Biology·Aleksandr VasilyevIain A Drummond
Sep 10, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·George D DemetriRobert G Maki
Oct 19, 2010·Cancer Research·Farbod ShojaeiJames G Christensen
Mar 6, 2013·Nature Reviews. Urology·Chao-Nan Qian
Aug 24, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Leonid L NikitenkoStephen B Fox
Nov 10, 2013·PloS One·Ilsiya IbragimovaPaul Cairns
Feb 4, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Dong NiXu Zhang
Feb 11, 2014·Current Opinion in Cell Biology·Morgan O'HayreJ Silvio Gutkind
Sep 16, 2014·Seminars in Cell & Developmental Biology·Katherine Stewart, Maxime Bouchard
Nov 2, 2014·EMBO Molecular Medicine·John Ml EbosRobert S Kerbel
Dec 17, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mariana VarnaGuilhem Bousquet
May 28, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Grant D StewartThomas Powles
Nov 1, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Keith A LawsonDonald G Morris
Jun 22, 2016·Nature Reviews. Urology·Maria I CarloRobert J Motzer
Oct 21, 2016·Journal of Experimental & Clinical Cancer Research : CR·Yanhui ZhangXueyi Dong
Nov 17, 2017·Nature Communications·Wang XiChwee Teck Lim

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