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Overcoming tumor resistance to anti-cancer agent TRAIL

Date:
March 22, 2010
Source:
Rockefeller University Press
Summary:
The TRAIL ligand is a promising anti-cancer 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 new study, small molecules known to block Mcl-1 might represent a suitable means to overcome TRAIL resistance.
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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 tumor cells for various reasons. Despite the expression of Bak, another protein 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 TRAIL.


Story Source:

The above post is reprinted from materials provided by Rockefeller University Press. Note: Materials may be edited for content and length.


Journal Reference:

  1. B. Gillissen, J. Wendt, A. Richter, A. Richter, A. Muer, T. Overkamp, N. Gebhardt, R. Preissner, C. Belka, B. Dorken, P. T. Daniel. Endogenous Bak inhibitors Mcl-1 and Bcl-xL: differential impact on TRAIL resistance in Bax-deficient carcinoma. The Journal of Cell Biology, 2010; 188 (6): 851 DOI: 10.1083/jcb.200912070

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Rockefeller University Press. "Overcoming tumor resistance to anti-cancer agent TRAIL." ScienceDaily. ScienceDaily, 22 March 2010. <www.sciencedaily.com/releases/2010/03/100322092045.htm>.
Rockefeller University Press. (2010, March 22). Overcoming tumor resistance to anti-cancer agent TRAIL. ScienceDaily. Retrieved August 4, 2015 from www.sciencedaily.com/releases/2010/03/100322092045.htm
Rockefeller University Press. "Overcoming tumor resistance to anti-cancer agent TRAIL." ScienceDaily. www.sciencedaily.com/releases/2010/03/100322092045.htm (accessed August 4, 2015).

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