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Updated: May 25, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Clear cell sarcoma of kidney: morphoproteomic analysis reveals genomic correlates and therapeutic options
Sagar Dhamne1, Robert E Brown, Michael Covinsky
1Baylor College of Medicine, Houston, TX, USA.
Abstract:
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 cyclin 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.
Insights
Clear cell sarcoma of kidney (CCSK) pathogenesis is explored using morphoproteomics. Cyclin D1 is identified as a key molecule, suggesting new therapeutic targets for this rare pediatric cancer.
Area of Science:
- Oncology
- Molecular Biology
- Pediatric Pathology
Background:
- Clear cell sarcoma of kidney (CCSK) is a rare pediatric renal tumor with unclear pathogenesis and diagnostic markers.
- Current treatments involve chemotherapy and radiation therapy, with doxorubicin showing improved survival rates.
Purpose of the Study:
- To analyze CCSK using a morphoproteomic approach.
- To elucidate the pathological mechanisms driving CCSK.
- To identify potential therapeutic targets and less-toxic chemotherapeutic agents.
Main Methods:
- Morphoproteomic analysis of three CCSK cases.
- Investigation of key molecular pathways including sonic hedgehog, nuclear factor-kappa B, and mTORC2/PI3K/Akt.
Main Results:
- Cyclin D1 is proposed as a central molecule in CCSK pathogenesis.
- Sonic hedgehog and nuclear factor-kappa B pathways are identified as primary drivers.
- mTORC2/PI3K/Akt pathway, heat shock protein 90, and phospholipase D1 are implicated as secondary mechanisms.
Conclusions:
- Cyclin D1, driven by specific molecular pathways, is crucial in CCSK development.
- Targeting these pathways with agents like statins, 13-cis retinoic acid, curcumin, and 17-AAG may offer less-toxic combinatorial treatment options.
