{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T21:08:19Z","timestamp":1775250499463,"version":"3.50.1"},"reference-count":53,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"4","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Homologous recombination deficiency (HRD) is a key determinant of sensitivity to DNA-damaging agents; however, its genomic characterization in colorectal cancer (CRC) remains limited. This study investigated whether low RNA expression of homologous recombination (HR) genes identifies patients with metastatic CRC who derive survival benefit from oxaliplatin- or irinotecan-based therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>A total of 22,957 metastatic CRC samples were subjected to DNA and RNA sequencing (Caris Life Sciences, Dallas, TX). Patients with microsatellite instability\u2013high or pathogenic HR gene mutations were excluded to define a HR-proficient cohort. Overall survival (OS) was compared between patients with low (bottom 25%) versus high (top 25%) RNA expression of HR genes after oxaliplatin or irinotecan exposure. Validation was performed in the PARADIGM phase III trial cohort (n = 262) of first-line modified fluorouracil, leucovorin, and oxaliplatin-treated patients with available RNAseq data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      In the discovery cohort, low expression of core HR genes correlated with significantly longer OS after oxaliplatin or irinotecan exposure, specifically\n                      <jats:italic toggle=\"yes\">RAD51<\/jats:italic>\n                      (43.0\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      36.3 months;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .005) and\n                      <jats:italic toggle=\"yes\">BLM<\/jats:italic>\n                      (42.9\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      34.2 months;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .005). Similar associations were observed for\n                      <jats:italic toggle=\"yes\">RAD51<\/jats:italic>\n                      <jats:italic toggle=\"yes\"\/>\n                      (28.1\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      22.9 months;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .02) and\n                      <jats:italic toggle=\"yes\">BLM<\/jats:italic>\n                      (29.1\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      23.2 months;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .005) in irinotecan-treated patients. In the PARADIGM validation cohort, low\n                      <jats:italic toggle=\"yes\">BLM<\/jats:italic>\n                      expression was associated with improved OS (41.5\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      22.4 months; HR = 0.52;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .002), whereas\n                      <jats:italic toggle=\"yes\">RAD51<\/jats:italic>\n                      showed a favorable but nonsignificant trend. These findings remained significant after adjustment for treatment arm, tumor sidedness, and metastatic burden.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Low\n                      <jats:italic toggle=\"yes\">BLM<\/jats:italic>\n                      RNA expression is associated with improved survival after treatment with DNA-damaging agents, whereas low\n                      <jats:italic toggle=\"yes\">RAD51<\/jats:italic>\n                      expression shows a favorable but nonsignificant trend. These findings are exploratory and suggest that RNA-based HR gene expression may warrant further investigation as a potential prognostic biomarker in metastatic CRC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-00452","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T19:59:13Z","timestamp":1775246353000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Survival in Patients With Low Expression of Wild-Type Homologous Recombination Genes: Refining the Homologous Recombination Paradigm in Colorectal Cancer"],"prefix":"10.1200","volume":"10","author":[{"given":"Daniel","family":"Walden","sequence":"first","affiliation":[{"name":"Department of Medical Oncology and Hematology, Mayo Clinic, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3354-308X","authenticated-orcid":true,"given":"Felipe","family":"Batalini","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, Mayo Clinic, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8057-0841","authenticated-orcid":true,"given":"Cody","family":"Eslinger","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, Mayo Clinic, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5241-6855","authenticated-orcid":true,"given":"Yoshiaki","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Krueger","sequence":"additional","affiliation":[{"name":"Oncology Therapeutic Area Unit, Takeda Pharmaceutical Company Ltd, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachin Kumar","family":"Deshmukh","sequence":"additional","affiliation":[{"name":"Caris Life Science, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazunori","family":"Yamanaka","sequence":"additional","affiliation":[{"name":"Oncology Therapeutic Area Unit, Takeda Pharmaceutical Company Ltd, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5922-5392","authenticated-orcid":true,"given":"Christina","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, Mayo Clinic, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6931-242X","authenticated-orcid":true,"given":"Mohamad Basam","family":"Sonbol","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, Mayo Clinic, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon","family":"Wu","sequence":"additional","affiliation":[{"name":"Caris Life Science, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne","family":"Xiu","sequence":"additional","affiliation":[{"name":"Caris Life Science, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7579-1175","authenticated-orcid":true,"given":"John","family":"Strickler","sequence":"additional","affiliation":[{"name":"Duke University Medical Center, Durham, NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2700-2658","authenticated-orcid":true,"given":"Mitesh J.","family":"Borad","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, Mayo Clinic, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0161-4018","authenticated-orcid":true,"given":"Daniel","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, Mayo Clinic, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5572-743X","authenticated-orcid":true,"given":"Kei","family":"Muro","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0489-4756","authenticated-orcid":true,"given":"Takayuki","family":"Yoshino","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7721-1699","authenticated-orcid":true,"given":"Tanios","family":"Bekaii-Saab","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, Mayo Clinic, Phoenix, AZ"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03445"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-0076-6"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00921-w"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00958"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.742139"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-11-0206"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-59671-3"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.21037\/cco-22-114"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-2080"},{"key":"e_1_3_6_11_2","article-title":"PARP inhibitor insensitivity to BRCA1\/2 monoallelic mutations in microsatellite instability-high cancers","author":"Sokol ES","unstructured":"Sokol ES, Jin DX, Fine A, et al: PARP inhibitor insensitivity to BRCA1\/2 monoallelic mutations in microsatellite instability-high cancers. JCO Precis Oncol 10.1200\/PO.21.00531","journal-title":"JCO Precis Oncol"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00388-9"},{"key":"e_1_3_6_13_2","article-title":"Pan-cancer analysis of BRCA1 and BRCA2 genomic alterations and their association with genomic instability as measured by genome-wide loss of heterozygosity","author":"Sokol ES","unstructured":"Sokol ES, Pavlick D, Khiabanian H, et al: Pan-cancer analysis of BRCA1 and BRCA2 genomic alterations and their association with genomic instability as measured by genome-wide loss of heterozygosity. JCO Precis Oncol 10.1200\/PO.19.00345","journal-title":"JCO Precis Oncol"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-39525-3"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2015-0319"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-1227"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-016-0351-x"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2024.114036"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12467"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-3635"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102923"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-018-0217-4"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-0749"},{"key":"e_1_3_6_24_2","article-title":"Homologous recombination deficiency landscape of breast cancers and real-world effectiveness of poly ADP-ribose polymerase inhibitors in patients with somatic BRCA1\/2, germline PALB2, or homologous recombination deficiency signature","author":"Batalini F","unstructured":"Batalini F, Madison RW, Sokol ES, et al: Homologous recombination deficiency landscape of breast cancers and real-world effectiveness of poly ADP-ribose polymerase inhibitors in patients with somatic BRCA1\/2, germline PALB2, or homologous recombination deficiency signature. JCO Precis Oncol 10.1200\/PO.23.00091","journal-title":"JCO Precis Oncol"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3934"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-19-0665"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14404"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2025.105768"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.1372"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.02151"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-022-00439-1"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14174332"},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-35092-w"},{"key":"e_1_3_6_34_2","article-title":"Prevalence of homologous recombination-related gene mutations across multiple cancer types","author":"Heeke AL","unstructured":"Heeke AL, Pishvaian MJ, Lynce F, et al: Prevalence of homologous recombination-related gene mutations across multiple cancer types. JCO Precis Oncol 10.1200\/PO.17.00286","journal-title":"JCO Precis Oncol"},{"key":"e_1_3_6_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djab169"},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-018-0066-6"},{"key":"e_1_3_6_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12477"},{"key":"e_1_3_6_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4292"},{"key":"e_1_3_6_39_2","article-title":"Pan-cancer analysis of copy-number features identifies recurrent signatures and a homologous recombination deficiency biomarker to predict poly (ADP-ribose) polymerase inhibitor response","author":"Moore JA","unstructured":"Moore JA, Chen KT, Madison R, et al: Pan-cancer analysis of copy-number features identifies recurrent signatures and a homologous recombination deficiency biomarker to predict poly (ADP-ribose) polymerase inhibitor response. JCO Precis Oncol 10.1200\/PO.23.00093","journal-title":"JCO Precis Oncol"},{"key":"e_1_3_6_40_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-0275"},{"key":"e_1_3_6_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2012.451"},{"key":"e_1_3_6_42_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2013.1868"},{"key":"e_1_3_6_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27907"},{"key":"e_1_3_6_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32516"},{"key":"e_1_3_6_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-023-00368-x"},{"key":"e_1_3_6_46_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-21-0774"},{"key":"e_1_3_6_47_2","doi-asserted-by":"publisher","DOI":"10.1200\/EDBK_389574"},{"key":"e_1_3_6_48_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201809172"},{"key":"e_1_3_6_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34982"},{"key":"e_1_3_6_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_3_6_51_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-023-02071-0"},{"key":"e_1_3_6_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1110s43"},{"key":"e_1_3_6_53_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_6_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0390-2"}],"container-title":["JCO Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/PO-25-00452","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T19:59:25Z","timestamp":1775246365000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/PO-25-00452"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":53,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1200\/PO-25-00452"],"URL":"https:\/\/doi.org\/10.1200\/po-25-00452","relation":{},"ISSN":["2473-4284"],"issn-type":[{"value":"2473-4284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-05-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-18","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2500452"}}