The SRC Inhibitor Dasatinib Induces Stem Cell-Like Properties in Head and Neck Cancer Cells that are Effectively Counteracted by the Mithralog EC-8042

Journal of Clinical Medicine
Francisco Hermida-PradoJuana M García-Pedrero

Abstract

The frequent dysregulation of SRC family kinases (SFK) in multiple cancers prompted various inhibitors to be actively tested in preclinical and clinical trials. Disappointingly, dasatinib and saracatinib failed to demonstrate monotherapeutic efficacy in patients with head and neck squamous cell carcinomas (HNSCC). Deeper functional and mechanistic knowledge of the actions of these drugs is therefore needed to improve clinical outcome and to develop more efficient combinational strategies. Even though the SFK inhibitors dasatinib and saracatinib robustly blocked cell migration and invasion in HNSCC cell lines, this study unveils undesirable stem cell-promoting functions that could explain the lack of clinical efficacy in HNSCC patients. These deleterious effects were targeted by the mithramycin analog EC-8042 that efficiently eliminated cancer stem cells (CSC)-enriched tumorsphere cultures as well as tumor bulk cells and demonstrated potent antitumor activity in vivo. Furthermore, combination treatment of dasatinib with EC-8042 provided favorable complementary anti-proliferative, anti-invasive, and anti-CSC functions without any noticeable adverse interactions of both agents. These findings strongly support combinational strateg...Continue Reading

References

Jan 1, 1993·The Journal of Clinical Investigation·M S TalamontiG E Gallick
May 29, 1998·Journal of Molecular and Cellular Cardiology·B K Slinker
Dec 15, 2000·Oncogene·R B Irby, T J Yeatman
Nov 2, 2001·Nature·T ReyaI L Weissman
Jun 27, 2003·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·T MasakiS Kuriyama
Jul 30, 2003·Cancer Metastasis Reviews·Justin M Summy, Gary E Gallick
Jun 2, 2004·Nature Reviews. Cancer·Timothy J Yeatman
Oct 19, 2004·Oncogene·Sarah J Parsons, J Thomas Parsons
Aug 16, 2005·Current Opinion in Cell Biology·Egle Avizienyte, Margaret C Frame
Oct 6, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Faye M JohnsonNicholas J Donato
Apr 28, 2009·Molecular Oncology·Tim P GreenGerard F Costello
May 28, 2010·Journal of Cancer Science & Therapy·Amanda Gatesman AmmerScott A Weed
Jun 29, 2010·Current Cancer Drug Targets·B ElsbergerJ Edwards
Apr 28, 2011·Cancer·Heather D BrooksVassiliki A Papadimitrakopoulou
Mar 31, 2012·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Sofía T MenéndezJuana M García-Pedrero
Apr 5, 2012·Critical Reviews in Oncogenesis·Helen Creedon, Valerie G Brunton
Mar 26, 2013·Journal of Cell Science·Marta CanelValerie G Brunton
Feb 22, 2014·Nature Reviews. Molecular Cell Biology·Samy LamouilleRik Derynck
Dec 17, 2014·Stem Cell Reports·Binwu TangLalage M Wakefield
Jan 22, 2015·Proceedings of the National Academy of Sciences of the United States of America·Youzhi LiChiang J Li
Jun 14, 2016·Scientific Reports·Lucia Martinez-CruzadoRene Rodriguez
Feb 9, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Francesca CitronGustavo Baldassarre
Mar 11, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christine M ParseghianScott Kopetz
Dec 1, 2017·Neoplasia : an International Journal for Oncology Research·Juan TorninRene Rodriguez
Dec 9, 2017·The Journal of Pharmacology and Experimental Therapeutics·Narumol BhummaphanPithi Chanvorachote
Mar 3, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Lia GoreC Michel Zwaan
Apr 15, 2018·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·M Ángeles VillarongaJuana M García-Pedrero

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Citations

Jul 21, 2020·Applied Microbiology and Biotechnology·Jan KormanecDagmar Homerova
Apr 3, 2021·Frontiers in Cell and Developmental Biology·Jingbin XuFasheng Li
Aug 13, 2021·Frontiers in Oncology·Giuliana CataraDaniela Spano
Sep 8, 2021·Journal of Nanobiotechnology·Óscar EstupiñánRené Rodríguez

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Methods Mentioned

BETA
PCR
electrophoresis
Assay
Xenografts
flow cytometry
xenograft

Software Mentioned

Image Studio Lite
ImageJ
PAST
image J
GraphPad Prism

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