Rhabdoid Tumor of Kidney (RTK) is recognized as one of the toughest and most aggressive kidney cancers found in children. Protheragen provides a comprehensive suite of services aimed at accelerating the development of novel diagnostics and therapeutics for Rhabdoid Tumor of the Kidney.
Overview of Rhabdoid Tumor of Kidney (RTK)
Rhabdoid Tumor of the Kidney (RTK) is an extremely rare and very aggressive cancer that occurs in children; its defining feature is the presence of rhabdoid cells-large, pale-staining cells with off-center nuclei, prominent nucleoli, and bright cytoplasm. Although papers describing the disease first appeared in 1978, the name we use now was formalized in 1981. RTK now represents roughly 0.9 to 4 percent of all pediatric kidney tumors. It most often strikes infants and toddlers, with an average diagnosis around 13 to 18 months and a slight bias in favor of boys, who outnumber girls about one-and-a-half to one. When symptoms appear, children usually show blood in the urine, a palpable belly mass, or unexplained stomach pain, leading many doctors to mistakenly label the tumor as Wilms' tumor instead. Even with surgery, chemotherapy, and radiation combined, the outlook remains grim, with overall survival at four years ranging from only 20 to 42 percent, and almost all children with spread eventually dying.
Fig.1 Pathological findings. (A) EMA (x200); (B) S-100 (x100); (C) INI-1 (x100); (D) Ki-67 (x200); (E) Vim (x40); (F) CK (x100). (Zhanghuang C.,
et al., 2021)
Pathogenesis of Rhabdoid Tumor of Kidney (RTK)
The development of rhabdoid tumors is tightly connected to genetic changes, most notably the loss of the SMARCB1 (also known as INI1) tumor-suppressor gene on chromosome 22q11.2. As a key player in chromatin remodeling, SMARCB1 helps keep gene activity in check. When this gene is mutated or deleted, INI1 protein disappears, marking the tumor as rhabdoid. Without working SMARCB1, normal cell cycles break down, leading to rapid growth and tumor formation.
Besides changes to SMARCB1, other genetic and epigenetic hits likely help rhabdoid tumors get started. For example, researchers have found that cases often show loss of a whole copy of chromosome 22 and may carry additional mutations. Together, these alterations fuel the tumor's aggressive behavior and contribute to its generally grim outlook.
Diagnostics Development for Rhabdoid Tumor of Kidney (RTK)
Imaging Techniques
- Ultrasound: Often the initial imaging modality used to detect renal masses in children. However, ultrasound lacks specificity for distinguishing RTK from other renal tumors.
- Computed Tomography (CT): Provides detailed images of renal tumors and can detect small tumors with subrenal hematoma/effusion. CT scans are crucial for staging and preoperative planning.
- Magnetic Resonance Imaging (MRI): Offers superior soft tissue contrast and is useful for detecting early small tumors and assessing tumor invasion into surrounding structures.
Molecular Diagnostics
- Immunohistochemistry (IHC): Used to detect the loss of INI1 protein expression, which is a diagnostic marker for RTK. IHC can also assess the expression of other markers such as vimentin, epithelial membrane antigen (EMA), and Ki-67, which provide additional prognostic information.
- Fluorescence In Situ Hybridization (FISH): Detects chromosomal abnormalities, such as deletions of the SMARCB1 locus on chromosome 22q11.2, which are common in RTK.
- Next-Generation Sequencing (NGS): Allows for comprehensive genetic profiling of RTK tumors, identifying mutations and alterations in multiple genes simultaneously. NGS can reveal novel therapeutic targets and guide personalized therapeutic strategies.
Therapeutics Development for Rhabdoid Tumor of Kidney (RTK)
- Chemotherapy
Vincristine, Doxorubicin, and Cyclophosphamide (VDC): A standard chemotherapy regimen used in the therapeutic of RTK. These agents work synergistically to induce tumor cell death.
Ifosfamide, Carboplatin, and Etoposide (ICE): Another effective chemotherapy combination for RTK. ICE has shown activity against metastatic RTK and is often used in combination with VDC.
Targeted Chemotherapy: Agents targeting specific molecular pathways involved in RTK pathogenesis, such as PI3K-Akt signaling inhibitors, are under investigation.
- Immunotherapy
Checkpoint Inhibitors: Drugs that block inhibitory checkpoints on T cells, enhancing their ability to recognize and kill tumor cells. While still in the early stages of investigation for RTK, checkpoint inhibitors hold promise for future therapy.
Adoptive T Cell Therapy: Involves the ex vivo expansion and activation of patient-derived T cells, which are then reinfused to target and eliminate tumor cells.
Table 1. Therapeutics of Rhabdoid Tumor of Kidney (RTK).
| Therapeutics |
Drug Name |
Mechanism |
Description |
Stage |
| Cytotoxic Chemotherapy |
Ifosfamide + Carboplatin + Etoposide (ICE) |
DNA cross-linking, topoisomerase II inhibition, platinum-induced DNA adducts |
Standard backbone regimen for RTK; used in alternating cycles with VDC. |
Approved |
| Cytotoxic Chemotherapy |
Vincristine + Doxorubicin + Cyclophosphamide (VDC) |
Microtubule inhibition, DNA intercalation, and alkylating agents |
Alternating regimen with ICE improves response rates in high-risk cases. |
Approved |
| Cytotoxic Chemotherapy |
Vincristine + Actinomycin-D + Cyclophosphamide (VAC) |
Microtubule inhibition, DNA transcription inhibition, and alkylating agents |
Used in some protocols as a third-line option. |
Approved |
| Targeted Therapy |
Tazemetostat (EZH2 Inhibitor) |
Inhibits EZH2 methyltransferase, restoring tumor suppressor gene expression |
Shows partial responses in INI-1-negative tumors. |
Phase II |
| Immunotherapy |
NA |
Checkpoint Inhibitors (e.g., PD-1/PD-L1 inhibitors) |
No RTK-specific data; under investigation in combination trials. |
Preclinical |
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 offers comprehensive preclinical therapeutics development services for RTK, leveraging cutting-edge technologies and a multidisciplinary approach. Our services encompass diagnostics development, drug discovery, and therapy optimization and development, tailored to meet the unique needs of RTK research.
Disease Models
- SMARCB1/INI1 Conditional Knockout (CKO) Mouse
- Patient-Derived Xenograft (PDX) Models
- Renal Capsule Engraftment Models
- Ferric Nitrotriacetate (Fe-NTA) Models
Protheragen provides customized services to address specific research questions and challenges in RTK. Our team of experts works closely with clients to design and execute tailored experiments, from target identification and validation to lead optimization and preclinical development. If you are interested in our services, please feel free to contact us.
References
- Zhanghuang, Chenghao, et al. "Clinical and molecular differentiation between malignant rhabdoid tumor of the kidney and normal tissue: a two-case report." Frontiers in Oncology 11 (2021): 659709.
- Li, Jing, et al. "Case analysis of 14 children with malignant rhabdoid tumor of the kidney." Cancer Management and Research (2021): 4865-4872.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
