Clear Cell Sarcoma of Kidney: Morphoproteomic Analysis Reveals Genomic Correlates and Therapeutic Options

We used the morphoproteomic approach to analyze clear cell sarcoma of kidney (CCSK), a rare pediatric renal tumor, for which the exact pathogenesis and reliable diagnostic markers remain inexplicable. The tumor, currently being treated with chemotherapy and radiation therapy before or after radical nephrectomy, has demonstrated improved survival rates after introduction of doxorubicin. Three cases of CCSK were studied. We attempted to decipher the possible pathological mechanisms involved in CCSK and to explore the therapeutic targets and plausible less-toxic chemotherapeutic agents. We propose that eye lin D1 may be a central molecule in the pathogenesis of CCSK, driven mainly by the sonic hedgehog and the nuclear factor–kappa B pathways and secondarily by the mammalian target of rapamycin complex mTORC2/PI3K/Akt pathway, heat shock protein 90, and possibly phospholipase D1. Inclusion of relatively less toxic but effective therapies in the form of statins, 13-cis retinoic acid, curcumin, and 17-AAG in the combinatorial treatment strategies, which can target the involved subcellular pathways, may be considered.

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