UA cloudflare authentication

 

Synergistic effect of eribulin and CDK inhibition for the treatment of triple negative breast cancer

Simple item page
dc.contributor.authorRao, Shreyas S.
dc.contributor.authorStoehr, Jenna
dc.contributor.authorDokic, Danijela
dc.contributor.authorWan, Lei
dc.contributor.authorDecker, Joseph T.
dc.contributor.authorKonopka, Kristine
dc.contributor.authorThomas, Alexandra L.
dc.contributor.authorWu, Jia
dc.contributor.authorKaklamani, Virginia G.
dc.contributor.authorShea, Lonnie D.
dc.contributor.authorJeruss, Jacqueline S.
dc.contributor.otherUniversity of Alabama Tuscaloosa
dc.contributor.otherNorthwestern University
dc.contributor.otherUniversity of Michigan
dc.contributor.otherUniversity of Texas Health Science Center at San Antonio
dc.date.accessioned2023-09-28T19:10:21Z
dc.date.available2023-09-28T19:10:21Z
dc.date.issued2017
dc.description.abstractActivation of CDK2 in triple negative breast cancer (TNBC) can contribute to non-canonical phosphorylation of a TGF beta signaling component, Smad3, promoting cell proliferation and migration. Inhibition of CDK2 was shown to decrease breast cancer oncogenesis. Eribulin chemotherapy was used effectively in the treatment of TNBC. To this end, we tested therapeutic efficacy of a novel CDK2/9 inhibitor, CYC065, eribulin, and the combination of CYC065 and eribulin in 3 different TNBC cell lines, and an in vivo xenograft model. Specifically, we characterized cell proliferation, apoptosis, migration, cell cycle associated protein expression, treatment-related transcription factor activity, and tumor growth in TNBC. Treatment with CYC065 and eribulin in combination had a superior effect on decreasing cell proliferation, inducing apoptosis, and inhibiting migration in TNBC cell lines in vitro. Combination therapy inhibited non-canonical Smad3 phosphorylation at the T179 site in the protein linker region, and resulted in increased p15 and decreased c-myc expression. In a transcription factor array, combination treatment significantly increased activity of AP1 and decreased activity of factors including NF kappa B, SP1, E2F, and SMAD3. In an in vivo xenograft model of TNBC, individual and combination treatments resulted in a decrease in both tumor volume and mitotic indices. Taken together, these studies highlight the potential of this novel drug combination, CYC065 and eribulin, to suppress the growth of TNBC cells in vitro and in vivo, warranting further clinical investigation.en_US
dc.format.mediumelectronic
dc.format.mimetypeapplication/pdf
dc.identifier.citationRao, S. S., Stoehr, J., Dokic, D., Wan, L., Decker, J. T., Konopka, K., Thomas, A. L., Wu, J., Kaklamani, V. G., Shea, L. D., & Jeruss, J. S. (2017). Synergistic effect of eribulin and CDK inhibition for the treatment of triple negative breast cancer. In Oncotarget (Vol. 8, Issue 48, pp. 83925–83939). Impact Journals, LLC. https://doi.org/10.18632/oncotarget.20202
dc.identifier.doi10.18632/oncotarget.20202
dc.identifier.orcidhttps://orcid.org/0000-0001-7914-4741
dc.identifier.orcidhttps://orcid.org/0000-0003-2754-721X
dc.identifier.orcidhttps://orcid.org/0000-0001-7649-0171
dc.identifier.orcidhttps://orcid.org/0000-0002-2152-2233
dc.identifier.urihttps://ir.ua.edu/handle/123456789/10969
dc.languageEnglish
dc.language.isoen_US
dc.publisherImpact Journals
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCDK2
dc.subjecteribulin
dc.subjectTGF beta
dc.subjectSmad3
dc.subjecttriple negative breast cancer
dc.subjectNF-KAPPA-B
dc.subjectCYCLIN-DEPENDENT KINASES
dc.subjectSMAD3 ACTIVITY
dc.subjectPHOSPHORYLATION
dc.subjectAPOPTOSIS
dc.subjectPALBOCICLIB
dc.subjectONCOGENESIS
dc.subjectACTIVATION
dc.subjectRESISTANCE
dc.subjectMECHANISM
dc.subjectOncology
dc.subjectCell Biology
dc.titleSynergistic effect of eribulin and CDK inhibition for the treatment of triple negative breast canceren_US
dc.typeArticle
dc.typetext

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
PMC5663565-oncotarget-08-83925.pdf
Size:
4 MB
Format:
Adobe Portable Document Format
Download

Collections

Research and Publications - Department of Health Science