Pub Date : 2026-01-13DOI: 10.1007/s13402-025-01140-y
Mingli Yang, Michael J Schell, Jesse J Salk, Jake Higgins, Michael Hipp, Lance Pflieger, Warren Jack Pledger, Timothy J Yeatman
Purpose: EGFR inhibitor (EGFRi) therapies have been FDA-approved for metastatic colorectal cancer (CRC). However, extended RAS/RAF testing required in the drug labels, identifies only non-responders, and only ~50% of selected patients respond to therapy, suggesting an unmet need to develop additional biomarkers.
Methods: We previously reported combined mutations in APC and TP53 as a potential positive biomarker to identify EGFRi-sensitive patients. By leveraging the TwinStrand Duplex Sequencing (DS) technology, this study developed an ultrasensitive 6-gene panel DS assay that adds a positive filter for APC(A) and TP53(P) mutations in addition to the negative KRAS(K), BRAF(B), and NRAS(N) mutation filters for EGFRi therapy.
Results: The 6-gene DS assay was analytically validated using reference cell lines (n = 9, individually sequenced to > 3,000x Duplex depth). The assay yielded exceptionally high assay performance on (1) accuracy, (2) sensitivity, (3) specificity and (4) precision. Application to fresh frozen (FF):FFPE paired tissues from 21 CRC patients demonstrates that the ultrasensitive DS assay can accurately detect additional "new" mutations at low allelic frequencies compared to a standard NGS method (13 of the 17 new mutations had < 10% VAF) that may ultimately be responsible for drug resistance. Furthermore, Kaplan-Meier analysis on Duplex-sequenced EGFRi FFPE samples showed that the third-line metastatic CRC patients harboring combined APC and TP53 mutations (AP/APK(N) versus others) tended to have longer TOT (6.65 versus 3.60 months, p = 0.048, n = 29).
Conclusion: These data suggest the potential of the 6-gene Duplex Sequencing assay to improve EGFRi patient selection and therapeutic outcomes.
{"title":"Development of an APC and TP53-based duplex sequencing assay to positively predict colorectal cancer response to anti-EGFR therapy.","authors":"Mingli Yang, Michael J Schell, Jesse J Salk, Jake Higgins, Michael Hipp, Lance Pflieger, Warren Jack Pledger, Timothy J Yeatman","doi":"10.1007/s13402-025-01140-y","DOIUrl":"10.1007/s13402-025-01140-y","url":null,"abstract":"<p><strong>Purpose: </strong>EGFR inhibitor (EGFRi) therapies have been FDA-approved for metastatic colorectal cancer (CRC). However, extended RAS/RAF testing required in the drug labels, identifies only non-responders, and only ~50% of selected patients respond to therapy, suggesting an unmet need to develop additional biomarkers.</p><p><strong>Methods: </strong>We previously reported combined mutations in APC and TP53 as a potential positive biomarker to identify EGFRi-sensitive patients. By leveraging the TwinStrand Duplex Sequencing (DS) technology, this study developed an ultrasensitive 6-gene panel DS assay that adds a positive filter for APC(A) and TP53(P) mutations in addition to the negative KRAS(K), BRAF(B), and NRAS(N) mutation filters for EGFRi therapy.</p><p><strong>Results: </strong>The 6-gene DS assay was analytically validated using reference cell lines (n = 9, individually sequenced to > 3,000x Duplex depth). The assay yielded exceptionally high assay performance on (1) accuracy, (2) sensitivity, (3) specificity and (4) precision. Application to fresh frozen (FF):FFPE paired tissues from 21 CRC patients demonstrates that the ultrasensitive DS assay can accurately detect additional \"new\" mutations at low allelic frequencies compared to a standard NGS method (13 of the 17 new mutations had < 10% VAF) that may ultimately be responsible for drug resistance. Furthermore, Kaplan-Meier analysis on Duplex-sequenced EGFRi FFPE samples showed that the third-line metastatic CRC patients harboring combined APC and TP53 mutations (AP/APK(N) versus others) tended to have longer TOT (6.65 versus 3.60 months, p = 0.048, n = 29).</p><p><strong>Conclusion: </strong>These data suggest the potential of the 6-gene Duplex Sequencing assay to improve EGFRi patient selection and therapeutic outcomes.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"49 1","pages":"23"},"PeriodicalIF":4.8,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12799675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The epigenetic regulator SETDB1 as a key component of cancer stem cells and drug resistance in primary liver cancer.","authors":"Maël Padelli, Christophe Desterke, Aurore Devocelle, Georges Uzan, Antoinette Lemoine, Julien Giron-Michel","doi":"10.1007/s13402-025-01157-3","DOIUrl":"10.1007/s13402-025-01157-3","url":null,"abstract":"","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"49 1","pages":"18"},"PeriodicalIF":4.8,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12775003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145910634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-06DOI: 10.1007/s13402-025-01156-4
Jia-Mei Wang, Ning Liu, Xue-Jing Wei, Fu-Ying Zhao, Chao Li, Hua-Qin Wang, Chuan Liu
{"title":"Correction to: Regulation of AUF1 alternative splicing by hnRNPA1 and SRSF2 modulate the sensitivity of ovarian cancer cells to cisplatin.","authors":"Jia-Mei Wang, Ning Liu, Xue-Jing Wei, Fu-Ying Zhao, Chao Li, Hua-Qin Wang, Chuan Liu","doi":"10.1007/s13402-025-01156-4","DOIUrl":"10.1007/s13402-025-01156-4","url":null,"abstract":"","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"49 1","pages":"17"},"PeriodicalIF":4.8,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12775065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145910481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-05DOI: 10.1007/s13402-025-01147-5
Wenlong Zhu, Chang Fan, Jiali Yao, Linlin Ji, Yihai Shi, Jin Ding, Yugang Zhuang, Li Wang
{"title":"Multi-omics profiling reveals that Scissor<sup>+</sup> epithelial cells regulate intrahepatic metastasis of HCC via remodeling the metastatic microenvironment.","authors":"Wenlong Zhu, Chang Fan, Jiali Yao, Linlin Ji, Yihai Shi, Jin Ding, Yugang Zhuang, Li Wang","doi":"10.1007/s13402-025-01147-5","DOIUrl":"10.1007/s13402-025-01147-5","url":null,"abstract":"","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"49 1","pages":"12"},"PeriodicalIF":4.8,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12769604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-05DOI: 10.1007/s13402-025-01131-z
Julia Dudkiewicz-Garbicz, Paweł K Włodarski
{"title":"CDK12 and CDK13 in oncology: from RNA regulation to therapeutic targeting.","authors":"Julia Dudkiewicz-Garbicz, Paweł K Włodarski","doi":"10.1007/s13402-025-01131-z","DOIUrl":"10.1007/s13402-025-01131-z","url":null,"abstract":"","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":"49 1","pages":"13"},"PeriodicalIF":4.8,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12769584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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