{"doi":"10.3390/cancers16081567","title":"Discovery of Novel Potential Prognostic Markers and Targeted Therapy to Overcome Chemotherapy Resistance in an Advanced-Stage Wilms Tumor","abstract":"<jats:p>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.</jats:p>","journal":"Cancers","year":2024,"id":644239,"datarank":0.2592694778795379,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.017853791014422835,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.017853791014422835,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":3,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1676693,"name":"Natakorn Nokchan","orcid":null,"position":1,"is_corresponding":false},{"id":1676694,"name":"Natthapon Khongcharoen","orcid":null,"position":2,"is_corresponding":false},{"id":1676695,"name":"Wison Laochareonsuk","orcid":null,"position":3,"is_corresponding":false},{"id":407145,"name":"Komwit Surachat","orcid":"0000-0001-7793-7561","position":4,"is_corresponding":false},{"id":1676697,"name":"Thirachit Chotsampancharoen","orcid":null,"position":5,"is_corresponding":false},{"id":1676699,"name":"Thanit Sila","orcid":null,"position":6,"is_corresponding":false},{"id":1235208,"name":"Surasak Sangkhathat","orcid":"0000-0003-3622-3233","position":7,"is_corresponding":false},{"id":1676690,"name":"Pongsakorn Choochuen","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Discovery of Novel Potential Prognostic Markers and Targeted Therapy to Overcome Chemotherapy Resistance in an Advanced-Stage Wilms Tumor","abstract":"<jats:p>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.</jats:p>","is_dataset_classified":null,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38672648","pmcid":"PMC11049388","openalex_id":"https://openalex.org/W4394952803","authors":[],"funders":[{"funder_name":"Fundamental Research Fund through Prince of Songkla University","grant_id":"NRIIS172177","title":null},{"funder_name":"Fundamental Research Fund through Prince of Songkla University","grant_id":"MED6505138S","title":null},{"funder_name":"Fundamental Research Fund through Prince of Songkla University","grant_id":"NRIIS178921","title":null},{"funder_name":"Fundamental Research Fund through Prince of Songkla University","grant_id":"HSRI 65-093","title":null}],"total_grants":4,"fwci":0.6572,"citation_percentile":0.64904655,"influential_citations":0,"citation_trend":[{"year":2025,"count":4}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2072-6694/16/8/1567/pdf?version=1713534832","host_type":"journal"},{"url":"https://www.mdpi.com/2072-6694/16/8/1567/pdf?version=1713534832","host_type":"publisher"},{"url":"https://www.mdpi.com/2072-6694/16/8/1567/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/cancers16081567","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38672648","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11049388","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11049388/pdf/cancers-16-01567.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11049388","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11049388?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Renal and related cancers","Renal cell carcinoma treatment"],"mesh_terms":[],"keywords":["Chemotherapy","Druggability","Drug resistance","Stage (stratigraphy)","Cancer research","Exome sequencing","Targeted therapy","Wilms' tumor","Oncology","Mutation","Medicine","Cancer","Disease","Gene","Internal medicine","Biology","Genetics","Biomarkers","Wilms Tumor","Chemotherapy Resistance","Somatic Mutation","Cancer Driver Mutation"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-09T00:42:10.600164Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}