Details

Autor(en) / Beteiligte

• Subbiah, Vivek
• Brown, Robert E
• Jiang, Yunyun
• Buryanek, Jamie
• Hayes-Jordan, Andrea
• Kurzrock, Razelle
• Anderson, Pete M

Titel

Morphoproteomic Profiling of the Mammalian Target of Rapamycin

Ist Teil von

• PloS one, 2013-07, Vol.8 (7), p.e68985

Ort / Verlag

Public Library of Science

Erscheinungsjahr

2013

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Desmoplastic small round cell tumor (DSRCT) is a rare sarcoma in adolescents and young adults. The hallmark of this disease is a EWS-WT1 translocation resulting from apposition of the Ewing's sarcoma (EWS) gene with the Wilms' tumor (WT1) gene. We performed morphoproteomic profiling of DSRCT (EWS-WT1), Ewing's sarcoma (EWS-FLI1) and Wilms' tumor (WT1) to better understand the signaling pathways for selecting future targeted therapies. This pilot study assessed patients with DSRCT, Wilms' tumor and Ewing's sarcoma. Morphoproteomics and immunohistochemical probes were applied to detect: p-mTOR (Ser2448); p-Akt (Ser473); p-ERK1/2 (Thr202/Tyr204); p-STAT3 (Tyr 705); and cell cycle-related analytes along with their negative controls. Morphoproteomic tumor analyses revealed constitutive activation of the mTOR pathway as evidenced by: (a) expression of phosphorylated (p)-mTOR, p-p70S6K; (b) mTORC 2 in EWS and DSRCT; (c) ERK signaling was seen in the advanced setting indicating these as resistance pathways to IGF1R related therapies. This is the first morphoproteomic study of such pathways in these rare malignancies and may have potential therapeutic implications. Further study using morphoproteomic assessments of these tumors are warranted.