id:"swepub:oai:lup.lub.lu.se:4afbcf43-1689-4376-b60f-2967e5a0ee21"
Search: id:"swepub:oai:lup.lub.lu.se:4afbcf43-1689-4376-b60f-2967e5a0ee21" > Vemurafenib Synergi...
- 1 of 1
- Previous record
- Next record
- To hitlist
Vemurafenib Synergizes with Nutlin-3 to Deplete Survivin and Suppresses Melanoma Viability and Tumor Growth
- Ji, Zhenyu (author)
- Kumar, Raj (author)
- Taylor, Michael (author)
- show more...
- Rajadurai, Anpuchchelvi (author)
- Marzuka-Alcala, Alexander (author)
- Chen, Y. Erin (author)
- Njauw, Ching-Ni Jenny (author)
- Flaherty, Keith (author)
- Tsao, Hensin (author)
- show less...
- (creator_code:org_t)
- 2013
- 2013
- English.
- In: Clinical Cancer Research. - 1078-0432. ; 19:16, s. 4383-4391
- Journal article (peer-reviewed)
Abstract
Subject headings
Close
- Purpose: For patients with advanced melanoma, primary and secondary resistance to selective BRAF inhibition remains one of the most critically compelling challenges. One rationale argues that novel biologically informed strategies are needed to maximally cripple melanoma cells up front before compensatory mechanisms emerge. As p53 is uncommonly mutated in melanoma, restoration of its function represents an attractive adjunct to selective BRAF inhibition. Experimental Design: Thirty-seven BRAF(V600E)-mutated melanoma lines were subjected to synergy studies in vitro using a combination of vemurafenib and nutlin-3 (Nt-3). In addition, cellular responses and in vivo efficacy were also determined. We also analyzed changes in the levels of canonical apoptotic/survival factors in response to vemurafenib. Results: Dual targeting of BRAF(V600E) and Hdm2 with vemurafenib and Nt-3, respectively, synergistically induced apoptosis and suppressed melanoma viability in vitro and tumor growth in vivo. Suppression of p53 in melanoma cells abrogated Nt-3's effects fully and vemurafenib's effects partially. A survey of canonical survival factors revealed that both vemurafenib and Nt-3 independently attenuated levels of the antiapoptotic protein, survivin. Genetic depletion of survivin reproduces the cytotoxic effects of the combination strategy. Conclusion: These results show preclinical feasibility for overcoming primary vemurafenib resistance by restoring p53 function. Moreover, it identifies survivin as one downstream mediator of the observed synergism and a potential secondary target. (C)2013 AACR.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
Find in a library
- Clinical Cancer Research (Search for host publication in LIBRIS)
To the university's database
- 1 of 1
- Previous record
- Next record
- To hitlist
Find more in SwePub
- By the author/editor
- Ji, Zhenyu
- Kumar, Raj
- Taylor, Michael
- Rajadurai, Anpuc ...
- Marzuka-Alcala, ...
- Chen, Y. Erin
- show more...
- Njauw, Ching-Ni ...
- Flaherty, Keith
- Jönsson, Göran B
- Tsao, Hensin
- show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Clinical Medicin ...
- and Cancer and Oncol ...
- Articles in the publication
- Clinical Cancer ...
- By the university
- Lund University
Search outside SwePub
- Extend your search to:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - National Library Systems
- LIBRIS.kb.se
