Choochuen, P.; Nokchan, N.; Khongcharoen, N.; Laochareonsuk, W.; Surachat, K.; Chotsampancharoen, T.; Sila, T.; Sangkhathat, S. Discovery of Novel Potential Prognostic Markers and Targeted Therapy to Overcome Chemotherapy Resistance in an Advanced-Stage Wilms Tumor. Cancers2024, 16, 1567.
Choochuen, P.; Nokchan, N.; Khongcharoen, N.; Laochareonsuk, W.; Surachat, K.; Chotsampancharoen, T.; Sila, T.; Sangkhathat, S. Discovery of Novel Potential Prognostic Markers and Targeted Therapy to Overcome Chemotherapy Resistance in an Advanced-Stage Wilms Tumor. Cancers 2024, 16, 1567.
Choochuen, P.; Nokchan, N.; Khongcharoen, N.; Laochareonsuk, W.; Surachat, K.; Chotsampancharoen, T.; Sila, T.; Sangkhathat, S. Discovery of Novel Potential Prognostic Markers and Targeted Therapy to Overcome Chemotherapy Resistance in an Advanced-Stage Wilms Tumor. Cancers2024, 16, 1567.
Choochuen, P.; Nokchan, N.; Khongcharoen, N.; Laochareonsuk, W.; Surachat, K.; Chotsampancharoen, T.; Sila, T.; Sangkhathat, S. Discovery of Novel Potential Prognostic Markers and Targeted Therapy to Overcome Chemotherapy Resistance in an Advanced-Stage Wilms Tumor. Cancers 2024, 16, 1567.
Abstract
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 are chemotherapy-resistant. Our analysis revealed four genes (ALPK2, C16orf96, PRKDC, and SVIL) that correlated with chemotherapy resistance and reduced disease-free survival in ad-vanced-stage WT. Additionally, we identified driver mutations in 55 genes within the chemo-therapy-resistant group, including 14 druggable cancer driver genes. Based on the mutation profile 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.
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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