{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T09:12:01Z","timestamp":1779527521335,"version":"3.53.1"},"reference-count":51,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2026,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Poly(adenosine diphosphate ribose) polymerase (PARP) is recruited to DNA damage sites along with epigenetic factors such as DNA methyltransferase 1 (DNMT1). Inhibitors of DNMT modulate reactive oxygen species (ROS)\u2010cyclic adenosine monophosphate (cAMP)\/Protein Kinase A signaling and induce a \u201cBRCAness phenotype\u201d that further sensitizes cells to PARPi. In preclinical studies, combined DNMTi\u00a0+\u00a0PARPi therapy was effective in both triple\u2010negative (TNBC) and hormone resistant (HRBC) models with intact BRCA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The authors conducted a phase 1 study combining the oral DNMTi ASTX727 with the PARPi talazoparib in patients with previously treated TNBC or HRBC. Patients with deleterious mutations of BRCA were excluded. A classical 3+3 design guided dose escalation\/de\u2010escalation, and 28 days constituted each cycle. Serial peripheral blood mononuclear cells (PBMCs) were analyzed for changes in methylation using the Infinium Methylation EPIC BeadChip and LINE1 sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty\u2010four evaluable patients were enrolled and treated in eight dose cohorts. Myelosuppression was common with grade &gt;3 neutropenia in 42% and grade 3 anemia and thrombocytopenia in 13%. Dose\u2010limiting toxicity was limited to neutropenia. Efficacy was assessed in 29 patients. There were no objective responses, six patients had stable disease persisting for &gt;4 months in three patients. LINE1 demethylation ranged from \u223c2%\u201310% and immune\u2010specific CpGs (methylation in immune cells) changed 1%\u20135% at day 15. Methylation changes were not dose\u2010dependent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ASTX727 plus talazoparib produces significant myelosuppression without other adverse events. Modest methylation changes in PBMCs were detected. There were no objective responses, but some heavily pretreated patients had stable disease for &gt;4 months despite the attenuated doses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.70407","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T17:33:29Z","timestamp":1776188009000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A phase 1 study of ASTX727 plus talazoparib in patients with triple\u2010negative or hormone resistant\/HER2\u2010negative metastatic breast cancer"],"prefix":"10.1002","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7125-883X","authenticated-orcid":false,"given":"Kathy D.","family":"Miller","sequence":"first","affiliation":[{"name":"Indiana University Melvin and Bren Simon Comprehensive Cancer Center  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9022-2229","authenticated-orcid":false,"given":"Alexandra","family":"Thomas","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Althouse","sequence":"additional","affiliation":[{"name":"Biostatistics and Health Data Science Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zang","sequence":"additional","affiliation":[{"name":"Biostatistics and Health Data Science Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Conder","sequence":"additional","affiliation":[{"name":"Indiana University Melvin and Bren Simon Comprehensive Cancer Center  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3683-6286","authenticated-orcid":false,"given":"Ryan","family":"Burgos","sequence":"additional","affiliation":[{"name":"Van Andel Institute  Grand Rapids Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan P.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Indiana University Melvin and Bren Simon Comprehensive Cancer Center  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6797-2758","authenticated-orcid":false,"given":"Tarah","family":"Ballinger","sequence":"additional","affiliation":[{"name":"Indiana University Melvin and Bren Simon Comprehensive Cancer Center  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Douglas","sequence":"additional","affiliation":[{"name":"Wake Forest University School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Ansley","sequence":"additional","affiliation":[{"name":"Wake Forest University School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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