Ibrutinib as a potential therapeutic option for HER2 overexpressing breast cancer - the role of STAT3 and p21.

Investigational New Drugs
Chandra Bose PrabaharanMeena Kishore Sakharkar

Abstract

Treatment response rates to current anticancer therapies for HER2 overexpressing breast cancer are limited and are associated with severe adverse drug reactions. Tyrosine kinases perform crucial roles in cellular processes by mediating cell signalling cascades. Ibrutinib is a recently approved Tyrosine Kinase Inhibitor (TKI) that has been shown be an effective therapeutic option for HER2 overexpressing breast cancer. The molecular mechanisms, pathways, or genes that are modulated by ibrutinib and the mechanism of action of ibrutinib in HER2 overexpressing breast cancer remain obscure. In this study, we have performed a kinome array analysis of ibrutinib treatment in two HER2 overexpressing breast cancer cell lines. Our analysis shows that ibrutinib induces changes in nuclear morphology and causes apoptosis via caspase-dependent extrinsic apoptosis pathway with the activation of caspases-8, caspase-3, and cleavage of PARP1. We further show that phosphorylated STAT3Y705 is upregulated and phosphorylated p21T145 is downregulated upon ibrutinib treatment. We propose that STAT3 upregulation is a passive response as a result of induction of DNA damage and downregulation of phosphorylated p21 is promoting cell cycle arrest and apoptos...Continue Reading

References

Aug 24, 2001·Nature·S M DhanasekaranA M Chinnaiyan
Nov 5, 2003·The Journal of Biological Chemistry·Vanesa GottifrediCarol Prives
May 25, 2005·International Journal of Medical Sciences·Manash K Paul, Anup K Mukhopadhyay
Feb 24, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lyndsay N HarrisEric P Winer
Feb 9, 2008·Genes & Development·Núria de la IglesiaAzad Bonni
Jul 18, 2008·Cancer Research·Si Tuen Lee-HoeflichHoward M Stern
Sep 2, 2008·Clinical Breast Cancer·Mohammad Jahanzeb
Sep 4, 2008·Molecular Systems Biology·David J LynnFiona S L Brinkman
Dec 24, 2008·Nature Reviews. Cancer·Jianming ZhangNathanael S Gray
Jan 22, 2009·Science Signaling·Shakiba JalalScott Napper
Jan 1, 2007·Archives of Pathology & Laboratory Medicine·Antonio C WolffUNKNOWN American Society of Clinical Oncology/College of American Pathologists
Dec 8, 2009·Gastroenterology·Monica MusteanuRobert Eferl
Jan 13, 2010·Experimental Cell Research·Tim J Kruser, Deric L Wheeler
Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Lee A HonigbergJoseph J Buggy
Jan 1, 2009·Breast Care·Christoph MundhenkeChristian Schem
Apr 1, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Doris SchnellerWolfgang Mikulits
Jun 21, 2011·The American Journal of Pathology·Hua WangBin Gao
Sep 2, 2011·The Oncologist·William IrvinDeborah K Mayer
Nov 1, 2011·Nature Biotechnology·Mindy I DavisPatrick P Zarrinkar
Apr 19, 2012·Science Signaling·Yue LiAnthony Kusalik
Jan 5, 2013·Proceedings of the National Academy of Sciences of the United States of America·Olga A TimofeevaAnatoly Dritschilo
May 10, 2013·Bioinformatics·Brett TrostAnthony Kusalik
Aug 6, 2013·Genes, Chromosomes & Cancer·Cheryl EifertDouglas S Conklin
Sep 28, 2013·Critical Reviews in Oncology/hematology·Ana LluchLaura García-Estévez
Oct 12, 2013·CA: a Cancer Journal for Clinicians·Carol DeSantisAhmedin Jemal
Mar 25, 2014·Nature Reviews. Cancer·Rudi W HendriksLaurens P Kil
Apr 20, 2014·Cancers·Richard L Carpenter, Hui-Wen Lo
Jan 1, 2012·Biomolecules·Hui Ling Ko, Ee Chee Ren
Jul 6, 2014·Cancers·Hai-Feng Zhang, Raymond Lai
Oct 7, 2014·Current Breast Cancer Reports·Ciara C O'Sullivan, Karen L Smith
Mar 3, 2015·Proceedings of the National Academy of Sciences of the United States of America·Idit Sagiv-BarfiRonald Levy
Jun 4, 2016·Molecular Cancer Therapeutics·Xianhui WangDouglas S Conklin
Sep 30, 2016·Molecular Cancer Therapeutics·Jun ChenLaurence Elias
May 10, 2017·Nucleic Acids Research·Weijun LuoCory Brouwer

❮ Previous
Next ❯

Citations

Jan 27, 2021·Journal of Drug Targeting·Anish KandelMeena Kishore Sakharkar

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis