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ONCOLOGY: Answers to age-old questions surrounding fat cell cancer
Myxoid round cell liposarcoma (MRCLS) is a cancerous tumor that typically arises in deep fat tissues of the limbs or abdomen. It was shown almost 20 years ago to be characterized by a chromosomal change that generates a fusion protein known as TLS:CHOP. Despite this, neither the cell from which MRCLS arise nor the mechanism(s) by which TLS:CHOP induces tumor formation have been definitively determined. A team of researchers led by Igor Matushansky, at Columbia University, New York, has now provided some answers to these questions; in doing so, they identified a potential new combination therapy for the treatment of MRCLS.
A compound isolated from the sea squirt Ecteinascidia turbinate, ET-743, is a highly effective therapy for patients with MRCLS, but how it works has not been determined. Using a new mouse model of MRCLS that they developed, Matushansky and colleagues found that expression of TLS:CHOP in endogenous mesenchymal stem cells led to the in vivo development of MRCLS and that ET-743 worked by decreasing expression of TLS:CHOP. Moreover, combining ET-743 treatment with administration of agonists of the protein PPAR-gamma improved survival of the mice. Matushansky and colleagues therefore suggest that ET-743 plus PPAR-gamma agonist could provide a rational combination for treating MRCLS.
TITLE: PPAR-gamma agonists enhance ET-743induced adipogenic differentiation in a transgenic mouse model of myxoid round ce
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Journal of Clinical Investigation