Targeting the intrinsic apoptosis pathway as a strategy for melanoma therapy

Mohana-Kumaran, Nethia, Hill, David S., Allen, John D. and Haass, Nikolas K. (2014) Targeting the intrinsic apoptosis pathway as a strategy for melanoma therapy. Pigment Cell and Melanoma Research, 27 4: 525-539. doi:10.1111/pcmr.12242


Author Mohana-Kumaran, Nethia
Hill, David S.
Allen, John D.
Haass, Nikolas K.
Title Targeting the intrinsic apoptosis pathway as a strategy for melanoma therapy
Journal name Pigment Cell and Melanoma Research   Check publisher's open access policy
ISSN 1755-1471
1755-148X
Publication date 2014-07-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1111/pcmr.12242
Volume 27
Issue 4
Start page 525
End page 539
Total pages 15
Place of publication Malden, MA, United States
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
Melanoma drug resistance is often attributed to abrogation of the intrinsic apoptosis pathway. Targeting regulators of apoptosis is thus considered a promising approach to sensitizing melanomas to treatment. The development of small-molecule inhibitors that mimic natural antagonists of either antiapoptotic members of the BCL-2 family or the inhibitor of apoptosis proteins (IAPs), known as BH3- or SMAC-mimetics, respectively, are helping us to understand the mechanisms behind apoptotic resistance. Studies using BH3-mimetics indicate that the antiapoptotic BCL-2 protein MCL-1 and its antagonist NOXA are particularly important regulators of BCL-2 family signaling, while SMAC-mimetic studies show that both XIAP and the cIAPs must be targeted to effectively induce apoptosis of cancer cells. Although most solid tumors, including melanoma, are insensitive to these mimetic drugs as single agents, combinations with other therapeutics have yielded promising results, and tests combining them with BRAF-inhibitors, which have already revolutionized melanoma treatment, are a clear priority.
Keyword Melanoma therapy
Drug resistance
Intrinsic apoptosis pathway
BH3-mimetic
MCL-1 antagonist
IAP antagonist
SMAC-mimetic
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2015 Collection
UQ Diamantina Institute Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 23 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 30 May 2014, 22:09:54 EST by Nikolas Haass on behalf of UQ Diamantina Institute