Clear Cell Sarcoma of the Kidney (CCSK) represents a significant challenge in pediatric oncology. Protheragen stands at the forefront of preclinical research, offering a comprehensive suite of services specifically tailored for the development of diagnostics and therapeutics for Clear Cell Sarcoma of the Kidney (CCSK).
Overview of Clear Cell Sarcoma of the Kidney (CCSK)
Clear cell sarcoma of the kidney (CCSK) is a rare tumor that shows up in kids, making up only about 5 percent of all childhood kidney cancers. It's the second most common primary kidney cancer in children, coming right after Wilms' tumor, and in the United States, doctors see roughly 20 new cases each year. The disease mostly strikes children younger than 10, with a median age at diagnosis around 36 months, and it shows a noticeable boy-to-girl ratio of about 2 to 1. In contrast to Wilms' tumor, CCSK tends to spread differently, often landing in the bones and the central nervous system; this pattern creates tougher challenges and usually results in a worse outlook, even when the therapy is very aggressive.
Fig.1 Microscopic pathological images and immunohistochemical results. (Cao M.,
et al., 2022)
Pathogenesis of Clear Cell Sarcoma of the Kidney (CCSK)
Nobody yet knows exactly how clear-cell sarcoma of the kidney (CCSK) starts, but researchers keep spotting the same rare genetic glitches in tumors. In most cases, an abnormal chromosome rearrangement involving the BCOR gene turns up, creating a small internal duplication that acts like a driving engine for the cancer. Because this change shows up almost exclusively in CCSK and not in other childhood kidney tumors, it serves as a useful marker for pathologists. A handful of tumors carry different fusion genes, such as YWHAE-NUTM2B/E, YWHAE-FAM22, or IRX2-TERT, but these appear far less often. Taken together, these lesions probably upset normal cell controls, pushing affected kidney cells to multiply uncontrollably and form a tumor mass. Still, how exactly these events hijack cellular machinery-and what type of precursor cells they arise from-remains an open question that demands more laboratory work.
Diagnostics Development for Clear Cell Sarcoma of the Kidney (CCSK)
Molecular and Genetic Diagnostics
Molecular and genetic diagnostics are increasingly important for the accurate diagnosis of CCSK. Immunohistochemistry is a valuable tool, with markers such as vimentin, Cyclin D1, and Bcl-2 showing high sensitivity and specificity for CCSK. The use of BCOR antibodies has also been shown to be highly sensitive and specific for CCSK, aiding in the differentiation from other renal neoplasms. Additionally, fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) can detect chromosomal translocations and gene fusions characteristic of CCSK, providing definitive molecular confirmation.
Imaging-Based Diagnostics
Imaging plays a pivotal role in the diagnosis and staging of CCSK. CT scans, particularly contrast-enhanced abdominal-pelvic CT, are essential for visualizing the tumor's size, location, and relationship to surrounding structures. Key imaging features that distinguish CCSK from other renal tumors, such as Wilms' tumor, include perinephric vessel engorgement and greater tumor enhancement. These features, along with the presence of necrosis and hemorrhage, can aid in the differential diagnosis. MRI may also be useful for assessing tumor invasion and metastatic disease.
Therapeutics Development for Clear Cell Sarcoma of the Kidney (CCSK)
- Chemotherapy
Chemotherapy plays a critical role in the multimodal therapy of CCSK. Anthracycline-based regimens, such as doxorubicin in combination with actinomycin D, cyclophosphamide, and vincristine, have shown efficacy in improving overall survival rates. However, the optimal chemotherapy regimen and duration of therapy remain areas of active investigation, particularly in adult patients, where data are limited.
- Targeted Therapies and Immunotherapies
Emerging targeted therapies and immunotherapies offer promise for the therapeutic of CCSK. Hypoxia-inducible factor-2α (HIF-2α) inhibitors, such as belzutifan, have shown activity in preclinical models and are being evaluated in clinical trials. Immunotherapies, including immune checkpoint inhibitors, are also being explored for their potential to enhance the anti-tumor immune response.
Table 1. Ongoing Clinical Trials of Hypoxia-Inducible Factor-2α. (Kase A. M., et al., 2023)
| Intervention |
Target |
Trial Type |
Estimated Completion Date |
Identifier |
Status |
| Belzutifan (standard dose vs. high dose) |
HIF-2α |
Phase 2 |
Oct-25 |
NCT04489771 |
Active, not recruiting |
| Belzutifan plus lenvatinib vs. cabozantinib |
HIF-2α |
Phase 3 |
Dec-24 |
NCT04586231 |
Recruiting |
| Belzutifan vs. everolimus |
HIF-2α |
Phase 3 |
Sep-25 |
NCT04195750 |
Active, not recruiting |
| Belzutifan + pembrolizumab vs. pembrolizumab + placebo |
HIF-2α |
Phase 3 |
Jan-30 |
NCT05239728 |
Recruiting |
| Pembrolizumab + belzutifan + lenvatinib or pembrolizumab/quavonlimab + lenvatinib vs. pembrolizumab + lenvatinib |
HIF-2α |
Phase 3 |
Oct-26 |
NCT04736706 |
Recruiting |
| NKT2152 |
HIF-2α |
Phase 1/2 |
Sep-26 |
NCT05119335 |
Recruiting |
| Belzutifan + cabozantinib |
HIF-2α |
Phase 2 |
Aug-25 |
NCT03634540 |
Recruiting |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen is at the forefront of developing innovative diagnostics and therapeutics for CCSK. Our comprehensive services encompass drug discovery and preclinical research, aimed at accelerating the translation of scientific discoveries into effective therapeutics.
Disease Models
- VhlΔ/ΔPbrm1Δ/Δ Models
- VhlΔ/ΔBap1Δ/- Models
- VhlΔ/ΔTrp53Δ/ΔRb1Δ/Δ Models
- FlcnΔ/- Models
- Myc Overexpression + VhlΔ/ΔCDKN2AΔ/Δ Models
- TFEB Overexpression Models
Protheragen recognizes that each drug development program is unique, requiring a flexible and tailored approach. Our customized services for CCSK preclinical development include bespoke assay development to investigate specific molecular pathways identified as crucial for CCSK pathogenesis. If you are interested in our services, please feel free to contact us.
References
- Cao, Mingxin, et al. "Clear cell sarcoma of the kidney in an adult: a case report and literature review." Translational Cancer Research 11.1 (2022): 288.
- Kase, Adam M., Daniel J. George, and Sundhar Ramalingam. "Clear cell renal cell carcinoma: from biology to treatment." Cancers 15.3 (2023): 665.
- Benedetti, Daniel J., et al. "Treatment and outcomes of clear cell sarcoma of the kidney: A report from the Children's Oncology Group studies AREN0321 and AREN03B2." Cancer 130.13 (2024): 2361-2371.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
