Overcoming tumor resistance to anti-cancer agent TRAIL

Mar 22, 2010

The TRAIL ligand is a promising anticancer agent that preferentially kills tumor cells without apparent damage to healthy cells. Many cancers exhibit resistance to TRAIL, however, thus limiting its therapeutic potential. According to a study in the March 22 issue of the Journal of Cell Biology, small molecules known to block Mcl-1 (induced myeloid leukemia cell differentiation protein) might represent a suitable means to overcome TRAIL resistance.

Researchers know that TRAIL-induced cell death entirely depends on the presence of Bax, which is a member of the proapoptotic Bcl-2 family of proteins and is often lost in cells for various reasons. Despite the expression of Bak, another that promotes dell death, Bax-deficient cells are resistant to TRAIL-induced death.

Peter Daniel (Humboldt University, Germany) and colleagues investigate the role of two Bcl-2 proteins—Mcl-1 and Bcl-xL—that keep Bak in check. The team's findings show that blocking Mcl-1 but not Bcl-xL overcame resistance to TRAIL-induced cell death in bax-deficient cells and enabled TRAIL to activate Bak. Blocking Bak inhibitors like Mcl-1 appears to be a promising strategy in limiting the resistance of cancers to .

Explore further: 'Hairclip' protein mechanism explained

More information: Gillissen, B., et al. 2010. J. Cell Biol. doi:10.1083/jcb.200912070

add to favorites email to friend print save as pdf

Related Stories

New therapeutic target for melanoma identified

Apr 16, 2009

A protein called Mcl-1 plays a critical role in melanoma cell resistance to a form of apoptosis called anoikis, according to research published this week in Molecular Cancer Research.

Recommended for you

Japanese scientist resigns over stem cell scandal

18 hours ago

A researcher embroiled in a fabrication scandal that has rocked Japan's scientific establishment said Friday she would resign after failing to reproduce results of what was once billed as a ground-breaking study on ...

'Hairclip' protein mechanism explained

Dec 18, 2014

Research led by the Teichmann group on the Wellcome Genome Campus has identified a fundamental mechanism for controlling protein function. Published in the journal Science, the discovery has wide-ranging implications for bi ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.