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Targeting The More Lethal Form Of The Cancer Rhabdomyosarcoma

Date:
May 26, 2009
Source:
Journal of Clinical Investigation
Summary:
Embryonal rhabdomyosarcoma (ERMS) and alveolar rhabdomyosarcoma (ARMS) are the most common forms of an aggressive muscle cancer that mostly affects children. Although ARMS is less common than ERMS, it is associated with a much higher rate of mortality. New research, showing that the protein ILK promotes the growth of ARMS cells but suppresses the growth of ERMS cells, provides hope that developing a therapy tailored to the ARMS form of the cancer might be possible.

Rhabdomyosarcoma (RMS) is an aggressive muscle cancer that mostly affects children. The most common forms of RMS are embryonal rhabdomyosarcoma (ERMS) and alveolar rhabdomyosarcoma (ARMS). Although ARMS is less common than ERMS, it is associated with a much higher rate of mortality. A therapy tailored to the ARMS form of RMS is therefore badly needed.

A team of researchers, at the Hospital for Sick Children, Toronto, and Monash Institute of Medical Research, Australia, has now provided hope that it might be possible to develop such a therapy by showing that the protein ILK promotes the growth of ARMS cells, whereas it suppresses the growth of ERMS cells.

The team, led by David Malkin and Gregory Hannigan, determined that the signaling protein JNK mediated these differing effects of ILK. Knocking down expression of ILK in ERMS cells induced activation of JNK and promoted tumor cell growth both in vitro and when the cells were transplanted into immunodeficient mice. Conversely, knocking down expression of ILK in ARMS cells abrogated both JNK signaling and tumor cell growth. Further analysis revealed that the protein product of the fusion gene that characterizes ARMS downregulated JNK1 expression, providing mechanistic insight into the opposing roles of ILK in ARMS and ERMS. The authors therefore suggest it should be possible to identify patients with ARMS who would benefit from an anticancer therapeutic that targets ILK.

In an accompanying commentary, Charles Keller and colleagues concur with the authors that targeting ILK might provide a therapeutic strategy tailored to the treatment of ARMS. However, they caution that further studies are needed, in part because of the high rate of misdiagnosis of ARMS versus ERMS.


Story Source:

The above story is based on materials provided by Journal of Clinical Investigation. Note: Materials may be edited for content and length.


Journal Reference:

  1. Adam D. Durbin et al. JNK1 determines the oncogenic or tumorsuppressive activity of the integrin-linked kinase in human rhabdomyosarcoma. Journal of Clinical Investigation, May 26, 2009

Cite This Page:

Journal of Clinical Investigation. "Targeting The More Lethal Form Of The Cancer Rhabdomyosarcoma." ScienceDaily. ScienceDaily, 26 May 2009. <www.sciencedaily.com/releases/2009/05/090526093938.htm>.
Journal of Clinical Investigation. (2009, May 26). Targeting The More Lethal Form Of The Cancer Rhabdomyosarcoma. ScienceDaily. Retrieved October 22, 2014 from www.sciencedaily.com/releases/2009/05/090526093938.htm
Journal of Clinical Investigation. "Targeting The More Lethal Form Of The Cancer Rhabdomyosarcoma." ScienceDaily. www.sciencedaily.com/releases/2009/05/090526093938.htm (accessed October 22, 2014).

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