Picking a poison for brain tumors: Arsenic

December 22, 2010

Arsenic is usually thought of as a poison. Despite this, it has been used in medicine for over 2000 years, and the arsenic compound arsenic trioxide (ATO) is FDA approved for the treatment of acute promyelocytic leukemia. Now, a team of researchers, led by Aykut Üren, at Georgetown University Medical Center, Washington, has generated data using human cancer cell lines that suggest that ATO might also be of benefit to individuals with certain brain tumors or connective tissue tumors.

Certain cancers, in particular brain tumors known as medulloblastomas and connective tissue tumors known as Ewing sarcoma, are characterized by inappropriate activation of a signaling pathway known as the Hh/GLI1 signaling pathway. The team found that GLI1-dependent growth of medulloblastoma and Ewing sarcoma cell lines was suppressed by ATO, which worked by inhibiting GLI1. Furthermore, ATO prevented GLI1-dependent human Ewing sarcoma cell lines from developing tumors upon transplantation into mice and improved survival in a clinically relevant spontaneous mouse model of medulloblastoma with activated Hh pathway signaling. The authors therefore suggest that ATO should be considered as potential therapeutic for the treatment of tumors that exhibit inappropriate Hh/GLI1 pathway activation.

In an accompanying commentary, Praveen Raju, at Weill Cornell Medical College, New York, notes that the data provide rationale for considering ATO as a therapy for cancers other than acute promyelocytic leukemia. However, he cautions Ewing sarcoma and medulloblastoma are predominantly tumors of childhood and the Hh pathway is crucial for both embryonic and postnatal development, so ATO inhibition of this pathway might have severe side effects in such patients.
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TITLE: Arsenic trioxide inhibits human cancer cell growth and tumor development in mice by blocking Hedgehog/GLI pathway

AUTHOR CONTACT:
Aykut Üren
Georgetown University Medical Center, Washington, DC, USA.
Phone: 202.687.9504; Fax: 202.687.1434; E-mail: au26@georgetown.edu.

View this article at: http://www.jci.org/articles/view/42874?key=b4953e0cf3401fb57e38

ACCOMPANYING COMMENTARY
TITLE: Arsenic: a potentially useful poison for Hedgehog-driven cancers

AUTHOR CONTACT:
G. Praveen Raju
Weill Cornell Medical College, New York, New York, USA.

Phone: 212.746.1279; Fax: 212.746.4001; E-mail: prr9001@med.cornell.edu.

View this article at: http://www.jci.org/articles/view/45692?key=d168085cd96838efb43b

JCI Journals

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