{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T06:35:18Z","timestamp":1778913318319,"version":"3.51.4"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"vor","delay-in-days":3807,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"European LeukemiaNet"},{"DOI":"10.13039\/100000174","name":"AIL","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000174","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"AIRC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"name":"PRIN"},{"DOI":"10.13039\/501100004740","name":"Fondazione del Monte di Bologna e Ravenna","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004740","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Learning Objectives<\/jats:title>\n                  <jats:p>After completing this course, the reader will be able to: Explain the IC50 of a tyrosine kinase inhibitor and the kind of information this parameter provides about its efficacy.List the multiple factors that may be responsible for resistance to a target therapeutic agent.Describe the clinical relevance of Bcr-Abl mutations in chronic myeloid leukemia patients.<\/jats:p>\n                  <jats:p>This article is available for continuing medical education credit at CME.TheOncologist.com<\/jats:p>\n                  <jats:p>Development of drug resistance to imatinib mesylate in chronic myeloid leukemia (CML) patients is often accompanied by selection of point mutations in the kinase domain (KD) of the Bcr-Abl oncoprotein, where imatinib binds. Several second-generation tyrosine kinase inhibitors (TKIs) have been designed rationally so as to enhance potency and retain the ability to bind mutated forms of Bcr-Abl. Since the preclinical phase of their development, most of these inhibitors have been tested in in vitro studies to assess their half maximal inhibitory concentration (IC50) for unmutated and mutated Bcr-Abl\u2014that is, the drug concentration required to inhibit the cell proliferation or the phosphorylation processes driven by either the unmutated or the mutated forms of the kinase. A number of such studies have been published, and now that two inhibitors\u2014dasatinib and nilotinib\u2014are available for the treatment of imatinib-resistant cases, it is tempting for clinicians to reason on the IC50 values to guess, case by case, which one will work best in patients harboring specific Bcr-Abl KD mutations. Here, we discuss the pros and cons of using this approach in TKI selection.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2010-0388","type":"journal-article","created":{"date-parts":[[2011,6,3]],"date-time":"2011-06-03T05:34:29Z","timestamp":1307079269000},"page":"868-876","source":"Crossref","is-referenced-by-count":42,"title":["Choosing the Best Second-Line Tyrosine Kinase Inhibitor in Imatinib-Resistant Chronic Myeloid Leukemia Patients Harboring Bcr-Abl Kinase Domain Mutations: How Reliable Is the IC50?"],"prefix":"10.1093","volume":"16","author":[{"given":"Simona","family":"Soverini","sequence":"first","affiliation":[{"name":"Department of Haematology\/Oncology, \u201cL. e A. Ser\u00edgnoli,\u201d University of Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianantonio","family":"Rosti","sequence":"additional","affiliation":[{"name":"Department of Haematology\/Oncology, \u201cL. e A. Ser\u00edgnoli,\u201d University of Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilaria","family":"Iacobucci","sequence":"additional","affiliation":[{"name":"Department of Haematology\/Oncology, \u201cL. e A. Ser\u00edgnoli,\u201d University of Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Baccarani","sequence":"additional","affiliation":[{"name":"Department of Haematology\/Oncology, \u201cL. e A. Ser\u00edgnoli,\u201d University of Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Department of Haematology\/Oncology, \u201cL. e A. Ser\u00edgnoli,\u201d University of Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,5,31]]},"reference":[{"key":"2021122401031060500_B1","first-page":"85","article-title":"Chromosome studies on normal and leukemic human leukocytes","volume":"25","author":"Nowell","year":"1960","journal-title":"J Natl Cancer Inst"},{"key":"2021122401031060500_B2","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/243290a0","article-title":"Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining","volume":"243","author":"Rowley","year":"1973","journal-title":"Nature"},{"key":"2021122401031060500_B3","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0092-8674(84)90077-1","article-title":"Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 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