{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:07:12Z","timestamp":1760234832924,"version":"build-2065373602"},"reference-count":172,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["RTI2018-094584-B-I00"],"award-info":[{"award-number":["RTI2018-094584-B-I00"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en C\u00e1ncer","award":["CB16\/12\/00334"],"award-info":[{"award-number":["CB16\/12\/00334"]}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["2017 SGR 1009"],"award-info":[{"award-number":["2017 SGR 1009"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Chronic lymphocytic leukemia (CLL) is characterized by a high degree of genetic variability and interpatient heterogeneity. In the last decade, novel alterations have been described. Some of them impact on the prognosis and evolution of patients. The approval of BTK inhibitors, PI3K inhibitors and Bcl-2 inhibitors has drastically changed the treatment of patients with CLL. The effect of these new targeted therapies has been widely analyzed in TP53-mutated cases, but few data exist about the response of patients carrying other recurrent mutations. In this review, we describe the biological pathways recurrently altered in CLL that might have an impact on the response to these new therapies together with the possibility to use new actionable targets to optimize treatment responses.<\/jats:p>","DOI":"10.3390\/cancers13133150","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T04:24:36Z","timestamp":1624508676000},"page":"3150","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Challenges with Approved Targeted Therapies against Recurrent Mutations in CLL: A Place for New Actionable Targets"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6756-1820","authenticated-orcid":false,"given":"Irene","family":"L\u00f3pez-Oreja","sequence":"first","affiliation":[{"name":"Experimental Therapies in Lymphoid Neoplasms, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Oncolog\u00eda (CIBERONC), 28029 Madrid, Spain"},{"name":"Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain"},{"name":"Universitat Pompeu Fabra, 08005 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3447-3848","authenticated-orcid":false,"given":"Heribert","family":"Playa-Albinyana","sequence":"additional","affiliation":[{"name":"Experimental Therapies in Lymphoid Neoplasms, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Oncolog\u00eda (CIBERONC), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4329-8834","authenticated-orcid":false,"given":"Fabi\u00e1n","family":"Arenas","sequence":"additional","affiliation":[{"name":"Experimental Therapies in Lymphoid Neoplasms, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Oncolog\u00eda (CIBERONC), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5545-0178","authenticated-orcid":false,"given":"M\u00f3nica","family":"L\u00f3pez-Guerra","sequence":"additional","affiliation":[{"name":"Experimental Therapies in Lymphoid Neoplasms, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Oncolog\u00eda (CIBERONC), 28029 Madrid, Spain"},{"name":"Hematopathology Section, Hospital Cl\u00ednic, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7486-8484","authenticated-orcid":false,"given":"Dolors","family":"Colomer","sequence":"additional","affiliation":[{"name":"Experimental Therapies in Lymphoid Neoplasms, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Oncolog\u00eda (CIBERONC), 28029 Madrid, Spain"},{"name":"Hematopathology Section, Hospital Cl\u00ednic, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nature10113","article-title":"Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia","volume":"475","author":"Puente","year":"2011","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nature14666","article-title":"Non-coding recurrent mutations in chronic lymphocytic leukaemia","volume":"526","author":"Puente","year":"2015","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/ng.1032","article-title":"Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia","volume":"44","author":"Quesada","year":"2011","journal-title":"Nat. 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