Biological Drivers of Wilms Tumor Prognosis and Treatment

Abstract

Prior to the 1950s, survival from Wilms tumor (WT) was less than 10%. Today, a child diagnosed with WT has a greater than 90% chance of survival. These gains in survival rates from WT are attributed largely to improvements in multimodal therapy: Enhanced surgical techniques leading to decreased operative mortality, optimization of more effective chemotherapy regimens (specifically, dactinomycin and vincristine), and inclusion of radiation therapy in treatment protocols. More recent improvements in survival, however, can be attributed to a growing understanding of the molecular landscape of Wilms tumor. Particularly, identification of biologic markers portending poor prognosis has facilitated risk stratification to tailor therapy that achieves the best possible outcome with the least possible toxicity. The aim of this review is to (1) outline the specific biologic markers that have been associated with prognosis in WT and (2) provide an overview of the current use of biologic and other factors to stratify risk and assign treatment accordingly.

<p>The coexistence of a Wilms&rsquo; tumor and renal cell carcinoma in children: a case report and review of the literature</p>

“…The treatment for WTs is multidisciplinary and involves surgery and chemotherapy, which is individualized based on risk stratification 15. Biological markers associated with a poor WT prognosis include LOH at 1p/16q, LOH at 11q, LOH at 4p and 14q, 1q gain, MYCN amplification, and TP53 and WT1 mutations 21,22. The prognosis of RCCs in children is poorer than that in WT cases, with an overall survival rate of 64%.…”

Uptake Transporters of the SLC21, SLC22A, and SLC15A Families in Anticancer Therapy—Modulators of Cellular Entry or Pharmacokinetics?

“…However, this variant was not significantly associated with act D PK. Act D is a polypeptide antibiotic and inhibitor of RNA polymerases used in the treatment of Wilms tumor, rhabdomyosarcoma, and Ewing's sarcoma [227][228][229][230][231]. Overall, the broad expression of PEPT1 and 2 in healthy organs and the redundancy in transport of "PEPT-specific" drugs, amino acids, and di-/tripeptides challenges the reasonable concept of PEPT-specific targeting or inhibition in tumors.…”

Insights into the Chemical Biology of Childhood Embryonal Solid Tumors by NMR-Based Metabolomics

“…This heterogeneity is also reflected in gene expression profiles [45] and genomic alterations [44] with impact in risk stratification and treatment response [46]. The studies in WT have tried to define the groups of patients of high and low risk, independently of the morphology and staging, using molecular markers [47][48][49]. The identified biomarkers have failed to give the consistent predictive information in regard to the clinical outcome of WT; however, data from NMR are scarce.…”