Cancers (Apr 2024)

Discovery of Novel Potential Prognostic Markers and Targeted Therapy to Overcome Chemotherapy Resistance in an Advanced-Stage Wilms Tumor

  • Pongsakorn Choochuen,
  • Natakorn Nokchan,
  • Natthapon Khongcharoen,
  • Wison Laochareonsuk,
  • Komwit Surachat,
  • Thirachit Chotsampancharoen,
  • Thanit Sila,
  • Surasak Sangkhathat

DOI
https://doi.org/10.3390/cancers16081567
Journal volume & issue
Vol. 16, no. 8
p. 1567

Abstract

Read online

Wilms tumor (WT), the most prevalent type of renal cancer in children, exhibits overall survival rates exceeding 90%. However, chemotherapy resistance, which occurs in approximately 10% of WT cases, is a major challenge for the treatment of WT, particularly for advanced-stage patients. In this study, we aimed to discover potential mutation markers and drug targets associated with chemotherapy resistance in advanced-stage WT. We performed exome sequencing to detect somatic mutations and molecular targets in 43 WT samples, comprising 26 advanced-stage WTs, of which 7 cases were chemotherapy-resistant. Our analysis revealed four genes (ALPK2, C16orf96, PRKDC, and SVIL) that correlated with chemotherapy resistance and reduced disease-free survival in advanced-stage WT. Additionally, we identified driver mutations in 55 genes within the chemotherapy-resistant group, including 14 druggable cancer driver genes. Based on the mutation profiles of the resistant WT samples, we propose potential therapeutic strategies involving platinum-based agents, PARP inhibitors, and antibiotic/antineoplastic agents. Our findings provide insights into the genetic landscape of WT and offer potential avenues for targeted treatment, particularly for patients with chemotherapy resistance.

Keywords