Show simple item record

dc.contributor.authorShaw, Greg
dc.contributor.authorProwse, David M.
dc.date.accessioned2015-07-02T13:51:37Z
dc.date.available2015-07-02T13:51:37Z
dc.date.issued2008-03-18
dc.identifier.citationShaw , G & Prowse , D M 2008 , ' Inhibition of androgen-independent prostate cancer cell growth is enhanced by combination therapy targeting Hedgehog and ErbB signalling ' , Cancer Cell International , vol. 8 , 3 . https://doi.org/10.1186/1475-2867-8-3
dc.identifier.otherPURE: 8695099
dc.identifier.otherPURE UUID: 1ecfba53-9de0-4b2c-a758-b3063e54116b
dc.identifier.otherScopus: 42449164689
dc.identifier.urihttp://hdl.handle.net/2299/16126
dc.description© 2008 Shaw and Prowse; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.description.abstractBackground: Prostate cancer is a leading cause of male cancer specific mortality. When cure by radical prostatectomy is not possible the next line of prostate cancer treatment is androgen deprivation. However prolonged androgen deprivation often results in relapse and androgen-independent prostate cancer that is inevitably fatal despite optimal chemotherapy. The Hedgehog signalling pathway has recently been implicated in prostate cancer development and metastasis. EGFR or ErbB2 expression has been also correlated with androgen independence, shorter survival and metastasis. Results: We determined that the Hedgehog and ErbB signalling pathways are active in circulating tumour cells isolated from androgen-independent prostate cancer patients and in the androgen-independent prostate cancer cell line LNCaP C4-2B. As a basis for synergistic chemotherapy protocols combinations of the Hedgehog specific inhibitor cyclopamine and the ErbB signalling inhibitors gefitinib or lapatinib were tested in this study. Androgen-independent prostate cancer cell growth was inhibited by a SMO inhibitor (cyclopamine) which blocks Hedgehog signalling and by ErbB inhibitors (gefitinib and lapatinib). The isobologram and combination index method of Chou and Talalay was used to evaluate drug interactions. Synergistic antiproliferation effects were observed when the Hedgehog and ErbB inhibitors were combined. Conclusion: Androgen-independent prostate cancer cell proliferation was associated with activity of the Hedgehog and ErbB signalling pathways. Cyclopamine, gefitinib or lapatinib treatment significantly decreased the proliferation of androgen-independent prostate cancer cells. The Hedgehog pathway therefore represents a promising new therapeutic target in androgen-independent prostate cancer. Synergistic effects were observed when Hedgehog and ErbB inhibitors were used together. This study may have clinical implications for improving the treatment of advanced prostate cancer.en
dc.language.isoeng
dc.relation.ispartofCancer Cell International
dc.rightsOpen
dc.subjectCancer Research
dc.subjectOncology
dc.titleInhibition of androgen-independent prostate cancer cell growth is enhanced by combination therapy targeting Hedgehog and ErbB signallingen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Life and Medical Sciences
dc.description.versiontypeFinal Published version
dcterms.dateAccepted2008-03-18
rioxxterms.versionVoR
rioxxterms.versionofrecordhttps://doi.org/10.1186/1475-2867-8-3
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.rights.accesstypeOpen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record