{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:35:46Z","timestamp":1790908546236,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2025,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Once considered an incurable disease with a poor prognosis (median survival, 3\u20136 years), chronic myeloid leukemia (CML) is now managed with a diverse clinical armamentarium that includes BCR::ABL1 tyrosine kinase inhibitors (TKIs), which have largely normalized life expectancy in most patients in the chronic phase of the disease (CML\u2010CP). Clinical challenges remain, including\n                    <jats:italic>ABL1<\/jats:italic>\n                    mutation\u2013driven treatment resistance (under the selection pressures exerted by TKIs), as well as treatment intolerance, which can involve potentially serious arterial occlusive events. Olverembatinib is a third\u2010generation TKI approved in China for TKI\u2010resistant CML\u2010CP and accelerated\u2010phase CML with the T135I mutation, as well as for CML\u2010CP resistant to or intolerant of first\u2010 and\/or second\u2010generation TKIs. Olverembatinib exhibits a broad coverage of\n                    <jats:italic>ABL1<\/jats:italic>\n                    mutants, including the gatekeeper T315I variant and compound mutations. In preclinical models, olverembatinib inhibited multiple downstream protein kinases, which has potentially opened avenues for future management of other malignancies, including acute myeloid and lymphoid leukemias, gastrointestinal tumors, and others. The pharmacokinetic profile of olverembatinib is compatible with alternate\u2010day dosing. In clinical trials, olverembatinib exerted potent antileukemic effects in heavily pretreated patients with CML, including those with ponatinib or asciminib resistance or intolerance, and was well tolerated. Future studies include the phase 3 registrational POLARIS\u20101 (NCT06051409; in patients with newly diagnosed Philadelphia chromosome\u2013positive acute lymphoblastic leukemia), POLARIS\u20102 (NCT06423911; in patients with CML with or without the T315I mutation), and POLARIS\u20103 (NCT06640361; in patients with succinate dehydrogenase\u2013deficient gastrointestinal stromal tumors) clinical trials.\n                  <\/jats:p>","DOI":"10.1002\/cncr.35832","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T12:26:56Z","timestamp":1744115216000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Olverembatinib in chronic myeloid leukemia\u2014Review of historical development, current status, and future research"],"prefix":"10.1002","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1908-3307","authenticated-orcid":false,"given":"Hagop","family":"Kantarjian","sequence":"first","affiliation":[{"name":"Department of Leukemia The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Zhai","sequence":"additional","affiliation":[{"name":"Ascentage Pharma Group Inc  Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian G.","family":"Oehler","sequence":"additional","affiliation":[{"name":"Translational Science and Therapeutics Division Fred Hutchinson Cancer Center  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer","family":"Jamy","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology Department of Medicine University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Koller","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation Division of Leukemia City of Hope National Medical Center  Duarte California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9702-8485","authenticated-orcid":false,"given":"Fadi G.","family":"Haddad","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9140-0610","authenticated-orcid":false,"given":"Koji","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4465-6119","authenticated-orcid":false,"given":"Elias J.","family":"Jabbour","sequence":"additional","affiliation":[{"name":"Department of Leukemia The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27443"},{"key":"e_1_2_15_3_1","unstructured":"Key Statistics for Chronic Myeloid Leukemia.American Cancer Society. 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