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Picking a poison for brain tumours: Arsenic
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 leukaemia. Now, a team of researchers, led by Aykut Ueren, at Georgetown University Medical Centre, Washington, has generated data using human cancer cell lines that suggest that ATO might also be of benefit to individuals with certain brain tumours or connective tissue tumours.
Certain cancers, in particular brain tumours known as medulloblastomas and connective tissue tumours known as Ewing sarcoma, are characterised by inappropriate activation of a signalling pathway known as the Hh/GLI1 signalling 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 tumours upon transplantation into mice and improved survival in a clinically relevant spontaneous mouse model of medulloblastoma with activated Hh pathway signalling. The authors therefore suggest that ATO should be considered as potential therapeutic for the treatment of tumours 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 leukaemia. However, he cautions Ewing sarcoma and medulloblastoma are predominantly tumours 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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