Pediatric cancer remains a troubling area of healthcare, particularly when speaking about the nephroblastoma tumor, also known as Wilms' tumor (WT). At Protheragen, we are dedicated to advancing the fight against nephroblastoma through comprehensive diagnostics and therapeutics development services.
Overview of Nephroblastoma
Nephroblastoma or Wilms' tumor is one of the most common cancers of the kidney in children and makes up 6-7% of all cancers found in children. The condition develops from embryonal kidney precursor cells and usually presents as an abdominal mass in children between the ages of two to five. Around 5–10 % of the cases are bilaterally affected with other genetic disorders such as WAGR (WT1 + PAX6 deletion), Beckwith-Wiedemann, and Denys-Drash syndrome. Histologically, the tumor displays a triphasic composition of blastemal, epithelial, and stromal elements, with predominant blastemal showing higher risk due to aggressive behavior.
Fig.1 Histopathological findings of Pediatric Extra-Renal Nephroblastoma (Wilms' Tumor). (Karim A.,
et al., 2023)
Pathogenesis of Nephroblastoma
Nephroblastoma is driven by genetic and epigenetic disruptions in renal development pathways:
- WT1 (11p13) and WT2 (11p15) mutations: Loss of WT1 function impairs nephrogenesis, while WT2 (IGF2/H19 locus) dysregulation leads to overgrowth phenotypes.
- Chromosomal aberrations: LOH at 1p and 16q are independent predictors of poor prognosis.
- Epigenetic silencing: Hypermethylation of tumor suppressor genes (e.g., CDKN2A) promotes proliferation.
- Developmental arrest: Persistent nephrogenic rests serve as precursor lesions, with 1 % progressing to nephroblastoma annually.
Diagnostics Development for Nephroblastoma
- Ultrasound (US): First-line modality for detecting renal masses; distinguishes solid vs. cystic lesions.
- MRI: Gold standard for staging, evaluating caval thrombi, and assessing bilateral disease.
- CT: Limited due to radiation exposure but useful for lung metastasis screening.
Molecular and Histopathology
- Next-generation sequencing (NGS): Identifies actionable mutations (e.g., TP53 in anaplastic variants).
- Liquid biopsy: Circulating tumor DNA (ctDNA) monitoring for minimal residual disease.
- Immunohistochemistry: WT1, CD56, and Ki-67 staining for risk stratification.
Therapeutics Development for Nephroblastoma
Recent advances in molecular biology have led to the development of targeted therapies and immunotherapies for nephroblastoma. These include:
- Monoclonal Antibodies: Target specific antigens expressed on the surface of tumor cells, leading to antibody-dependent cellular cytotoxicity.
- Small Molecule Inhibitors: Target specific signaling pathways involved in tumor growth and survival, such as the VEGF or mTOR pathways.
- CAR-T Cell Therapy: Engineered T cells that express chimeric antigen receptors (CARs) specific to tumor antigens, providing a potent and specific immune response against the tumor.
Table 1. Therapeutics of Nephroblastoma.
| Therapeutics |
Drug Name |
Target |
Description |
Stage |
| Chemotherapy |
Vincristine (VCR) |
Microtubule |
Disrupts mitotic spindle formation; backbone of all modern regimens |
Approved |
| Chemotherapy |
Actinomycin D (ACT-D) |
DNA |
Inhibits RNA synthesis; used with VCR in low-risk disease |
Approved |
| Chemotherapy |
Doxorubicin (DOX) |
DNA |
Added for stage III/IV or unfavorable histology |
Approved |
| Chemotherapy |
Cyclophosphamide |
DNA |
Used with DOX for high-risk/metastatic disease |
Approved |
| Chemotherapy |
Etoposide |
DNA |
Second-line or high-risk regimens (e.g., SIOP 2001) |
Approved |
| Chemotherapy |
Carboplatin |
DNA |
Substituted for cisplatin in some protocols (e.g., SIOP 2001) |
Approved |
| Chemotherapy |
Ifosfamide |
DNA |
High-risk/relapsed disease (e.g., NWTS-5) |
Approved |
| Targeted Therapy |
IGF-1R inhibitors |
IGF-1 receptor |
For relapsed/refractory disease |
Preclinical |
| Targeted Therapy |
mTOR inhibitors |
mTOR pathway |
For high-risk disease |
Preclinical |
| Immunotherapy |
Anti-GD2 monoclonal antibodies |
GD2 ganglioside |
Investigational for anaplastic subtypes |
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's diagnostics and therapeutics development services are distinguished by their interdisciplinary nature, integrating cutting-edge scientific expertise with advanced technological platforms. We provide comprehensive solutions that span the entire preclinical spectrum, from initial discovery and target validation to preclinical studies.
Disease Models
- Spontaneous Nephroblastoma Animal Models
- Wt1–/flH19+/–m Models
- MYCN Overexpression Models
- LIN28B Overexpression Models
- Patient-Derived Xenograft (PDX) Models
Recognizing that each drug development program has unique requirements, Protheragen offers highly customized services. Our team of biological experts collaborates closely with clients to design bespoke research plans that align with specific project goals and timelines. If you are interested in our services, please feel free to contact us.
References
- Karim, Akzhol, et al. "Pediatric extra-renal nephroblastoma (Wilms' tumor): a systematic case-based review." Cancers 15.9 (2023): 2563.
- Pietras, Wojciech. "Advances and changes in the treatment of children with nephroblastoma." Adv Clin Exp Med 21.6 (2012): 809-820.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
