Enzastaurin has anti-tumour effects in lung cancers with overexpressed JAK pathway molecules.

British Journal of Cancer
T ShimokawaA Gemma

Abstract

Enzastaurin, an oral serine-threonine kinase inhibitor, was initially developed as an ATP-competitive selective inhibitor against protein kinase Cβ. However, the mechanism by which enzastaurin contributes to tumourigenesis remains unclear. We analysed the anti-tumour effects of enzastaurin in 22 lung cancer cell lines to ascertain the potential for enzastaurin-based treatment of lung cancer. To identify molecules or signalling pathways associated with this sensitivity, we conducted a gene, receptor tyrosine kinases phosphorylation and microRNA expression profiling study on the same set of cell lines. We identified eight genes by pathway analysis of molecules having gene-drug sensitivity correlation, and used them to build a support vector machine algorithm model by which sensitive cell lines were distinguished from resistant cell lines. Pathway analysis revealed that the JAK/STAT signalling pathway was one of the main ones involved in sensitivity to enzastaurin. Overexpression of JAK1 was observed in the sensitive cells by western blotting. Simultaneous administration of enzastaurin and JAK inhibitor inhibited enzastaurin-induced cell growth-inhibitory effect. Furthermore, lentiviral-mediated JAK1-overexpressing cells were more...Continue Reading

References

Aug 15, 1997·European Journal of Biochemistry·E Livneh, D D Fishman
Mar 21, 1998·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·R Salgia, A T Skarin
Jan 11, 2002·The New England Journal of Medicine·Joan H SchillerUNKNOWN Eastern Cooperative Oncology Group
May 17, 2003·Bioorganic & Medicinal Chemistry Letters·Margaret M FaulMichael Mohr
Nov 1, 2003·Cancer Chemotherapy and Pharmacology·Kristan A KeyesBeverly A Teicher
Jun 10, 2005·Nature·Jun LuTodd R Golub
Aug 4, 2005·The Journal of Thoracic and Cardiovascular Surgery·Philip A RascoeW Roy Smythe
Dec 3, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Eric B HauraGerold Bepler
Feb 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Stefano VoliniaCarlo M Croce
Mar 15, 2006·Cancer Cell·Nozomu YanaiharaCurtis C Harris
Aug 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jeany M Rademaker-LakhaiEmile E Voest
Mar 4, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Yun OhGerold Bepler
Jul 31, 2008·British Journal of Cancer·T GelardiG Tortora
May 29, 2009·CA: a Cancer Journal for Clinicians·Ahmedin JemalMichael J Thun
Jul 15, 2009·Proceedings of the National Academy of Sciences of the United States of America·Masahiro SeikeCurtis C Harris
Aug 21, 2009·The New England Journal of Medicine·Tony S MokMasahiro Fukuoka
Nov 11, 2009·Annals of Oncology : Official Journal of the European Society for Medical Oncology·B GlimeliusP Pfeiffer
Dec 4, 2009·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Ignace VergoteJalid Sehouli
Jan 22, 2010·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Alberto ChiapporiJoachim von Pawel
Jun 25, 2010·The New England Journal of Medicine·Makoto MaemondoUNKNOWN North-East Japan Study Group
Aug 26, 2010·British Journal of Cancer·A KörnerH Allgayer

❮ Previous
Next ❯

Citations

Dec 1, 2012·Archives of Pathology & Laboratory Medicine·Philip T Cagle, Timothy Craig Allen
Sep 3, 2013·Archives of Pathology & Laboratory Medicine·Philip T CagleRandall J Olsen
Jan 20, 2016·International Journal of Oncology·Nobuhiko NishijimaAkihiko Gemma
Apr 26, 2017·Oncology Reports·Masahiro SeikeAkihiko Gemma
Apr 10, 2014·International Journal of Oncology·Susumu TakeuchiAkihiko Gemma

❮ Previous
Next ❯

Methods Mentioned

BETA
electrophoresis
transfection
xenograft
gene-chip

Software Mentioned

GeneChip Operating
Pathway Architect
Affymetrix GeneChip
ArrayAssist
Microarray Database

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.