Mutated FGFR4 protein helps a childhood cancer spread

Oct 05, 2009

Rhabdomyosarcoma (RMS) is a childhood cancer thought to originate from skeletal muscle. In patients whose disease has spread (metastasized) from the initial tumor site the chance of long-term survival is poor. Hopes for a therapy for such patients are not high, as little is known about the factors that control tumor progression and metastasis.

However, Javed Khan and colleagues, at the National Institute, Bethesda, have now determined that the protein FGFR4 has a role in RMS progression and have data suggesting that it might be a good for the treatment of individuals with RMS.

In the study, higher levels of expression of the FGFR4 gene were found to be associated with advanced-stage cancer and poor survival.

Conversely, reducing FGFR4 expression in a human RMS cell line decreased its ability to grow and metastasize when transplanted into mice. Further analysis identified mutations in the FGFR4 gene in 7.5% of human RMS tumor samples analyzed. When two of the FGFR4 mutants generated by these were analyzed further, they were found to be constitutively activated forms of FGFR4 that increased the proliferative, invasive, and metastatic capacities of a murine RMS cell line.

Importantly, treatment with a pharmacologic inhibitor of FGFRs made the murine RMS cells expressing the FGFR4 mutants very susceptible to death, leading the authors to suggest that targeting FGFR4 might be of therapeutic benefit in RMS.

More information: View this article at: www.jci.org/articles/view/3970… 140858eba01ab916a067

Source: Journal of Clinical Investigation

Explore further: Black men less willing to be investigated for prostate cancer

add to favorites email to friend print save as pdf

Related Stories

Novel cancer gene accelerates or stops tumour growth

May 27, 2009

(PhysOrg.com) -- Researchers at the Hospital for Sick Children (SickKids) and the University of Toronto have found a gene that plays a crucial role in the development of rhabdomyosarcoma - the most common childhood sarcoma ...

Recommended for you

US women's awareness of breast density varies

10 hours ago

Disparities in the level of awareness and knowledge of breast density exist among U.S. women, according to the results of a Mayo Clinic study published in the Journal of Clinical Oncology.

Study shows why some brain cancers resist treatment

11 hours ago

Scientists at The University of Texas MD Anderson Cancer Center may have discovered why some brain cancer patients develop resistance to standard treatments including radiation and the chemotherapy agent temozolomide.

Researchers identify genes responsible for lung tumors

13 hours ago

The lung transcription factor Nkx2-1 is an important gene regulating lung formation and normal respiratory functions after birth. Alterations in the expression of this transcription factor can lead to diseases such as lung ...

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.