dc.contributor.author |
Chernikova, Sophia B |
en |
dc.contributor.author |
Nguyen, Rochelle B |
en |
dc.contributor.author |
Truong, Jessica T |
en |
dc.contributor.author |
Mello, Stephano S |
en |
dc.contributor.author |
Stafford, Jason H |
en |
dc.contributor.author |
Hay, Michael |
en |
dc.contributor.author |
Olson, Andrew |
en |
dc.contributor.author |
Solow-Cordero, David E |
en |
dc.contributor.author |
Wood, Douglas J |
en |
dc.contributor.author |
Henry, Solomon |
en |
dc.contributor.author |
von Eyben, Rie |
en |
dc.contributor.author |
Deng, Lei |
en |
dc.contributor.author |
Gephart, Melanie Hayden |
en |
dc.contributor.author |
Aroumougame, Asaithamby |
en |
dc.contributor.author |
Wiese, Claudia |
en |
dc.contributor.author |
Game, John C |
en |
dc.contributor.author |
Győrffy, Balázs |
en |
dc.contributor.author |
Brown, J Martin |
en |
dc.date.accessioned |
2019-02-28T21:50:54Z |
en |
dc.date.issued |
2018-12 |
en |
dc.identifier.citation |
Journal of clinical investigation 128(12):5307-5321 Dec 2018 |
en |
dc.identifier.issn |
0021-9738 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/45644 |
en |
dc.description.abstract |
After the initial responsiveness of triple-negative breast cancers (TNBCs) to chemotherapy, they often recur as chemotherapy-resistant tumors, and this has been associated with upregulated homology-directed repair (HDR). Thus, inhibitors of HDR could be a useful adjunct to chemotherapy treatment of these cancers. We performed a high-throughput chemical screen for inhibitors of HDR from which we obtained a number of hits that disrupted microtubule dynamics. We postulated that high levels of the target molecules of our screen in tumors would correlate with poor chemotherapy response. We found that inhibition or knockdown of dynamin 2 (DNM2), known for its role in endocytic cell trafficking and microtubule dynamics, impaired HDR and improved response to chemotherapy of cells and of tumors in mice. In a retrospective analysis, levels of DNM2 at the time of treatment strongly predicted chemotherapy outcome for estrogen receptor-negative and especially for TNBC patients. We propose that DNM2-associated DNA repair enzyme trafficking is important for HDR efficiency and is a powerful predictor of sensitivity to breast cancer chemotherapy and an important target for therapy. |
en |
dc.format.medium |
Print-Electronic |
en |
dc.language |
eng |
en |
dc.relation.ispartofseries |
The Journal of clinical investigation |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
CHO Cells |
en |
dc.subject |
Animals |
en |
dc.subject |
Humans |
en |
dc.subject |
Cricetulus |
en |
dc.subject |
Mice |
en |
dc.subject |
Mice, Nude |
en |
dc.subject |
Dynamins |
en |
dc.subject |
Antineoplastic Agents |
en |
dc.subject |
Xenograft Model Antitumor Assays |
en |
dc.subject |
Female |
en |
dc.subject |
Recombinational DNA Repair |
en |
dc.subject |
Triple Negative Breast Neoplasms |
en |
dc.title |
Dynamin impacts homology-directed repair and breast cancer response to chemotherapy. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1172/jci87191 |
en |
pubs.issue |
12 |
en |
pubs.begin-page |
5307 |
en |
pubs.volume |
128 |
en |
dc.rights.holder |
Copyright: American Society for Clinical Investigation |
en |
pubs.end-page |
5321 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
Research Support, Non-U.S. Gov't |
en |
pubs.subtype |
research-article |
en |
pubs.subtype |
Journal Article |
en |
pubs.subtype |
Research Support, N.I.H., Extramural |
en |
pubs.elements-id |
758775 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Auckland Cancer Research |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
dc.identifier.eissn |
1558-8238 |
en |
pubs.record-created-at-source-date |
2018-10-30 |
en |
pubs.dimensions-id |
30371505 |
en |