دورية أكاديمية
Targeting Ikaros and Aiolos: reviewing novel protein degraders for the treatment of multiple myeloma, with a focus on iberdomide and mezigdomide.
| العنوان: | Targeting Ikaros and Aiolos: reviewing novel protein degraders for the treatment of multiple myeloma, with a focus on iberdomide and mezigdomide. |
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| المؤلفون: | Liu Y; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA, USA., Mo CC; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA, USA., Hartley-Brown MA; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA, USA.; Division of Hematology, Brigham and Women's Hospital, Boston, MA, USA., Sperling AS; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA, USA.; Division of Hematology, Brigham and Women's Hospital, Boston, MA, USA., Midha S; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA, USA.; Division of Hematology, Brigham and Women's Hospital, Boston, MA, USA., Yee AJ; Massachusetts General Cancer Center, Harvard Medical School, Boston, MA, USA., Bianchi G; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA, USA.; Division of Hematology, Brigham and Women's Hospital, Boston, MA, USA., Piper C; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA, USA., Tattersall A; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA, USA., Nadeem O; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA, USA., Laubach JP; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA, USA., Richardson PG; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA, USA. |
| المصدر: | Expert review of hematology [Expert Rev Hematol] 2024 Aug; Vol. 17 (8), pp. 445-465. Date of Electronic Publication: 2024 Jul 27. |
| نوع المنشور: | Journal Article; Review |
| اللغة: | English |
| بيانات الدورية: | Publisher: Taylor & Francis Country of Publication: England NLM ID: 101485942 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1747-4094 (Electronic) Linking ISSN: 17474094 NLM ISO Abbreviation: Expert Rev Hematol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2015- : Abingdon, Oxford : Taylor & Francis Original Publication: London : Expert Reviews |
| مواضيع طبية MeSH: | Multiple Myeloma*/drug therapy , Multiple Myeloma*/metabolism , Ikaros Transcription Factor*/metabolism , Thalidomide*/therapeutic use , Thalidomide*/analogs & derivatives , Thalidomide*/pharmacology, Humans ; Signaling Lymphocytic Activation Molecule Family/metabolism ; Signaling Lymphocytic Activation Molecule Family/antagonists & inhibitors ; Ubiquitin-Protein Ligases/metabolism ; Antineoplastic Agents/therapeutic use ; Antineoplastic Agents/pharmacology ; Proteolysis/drug effects ; Molecular Targeted Therapy ; Immunomodulating Agents/therapeutic use ; Immunomodulating Agents/pharmacology ; Clinical Trials as Topic ; Animals ; Piperidones ; Morpholines ; Receptors, Interleukin-17 ; Adaptor Proteins, Signal Transducing ; Phthalimides |
| مستخلص: | Introduction: The treatment of multiple myeloma (MM) is evolving rapidly. Quadruplet regimens incorporating proteasome inhibitors, immunomodulatory drugs (IMiDs), and CD38 monoclonal antibodies have emerged as standard-of-care options for newly diagnosed MM, and numerous novel therapies have been approved for relapsed/refractory MM. However, there remains a need for novel options in multiple settings, including refractoriness to frontline standards of care. Areas Covered: Targeting degradation of IKZF1 and IKZF3 - Ikaros and Aiolos - through modulation of cereblon, an E3 ligase substrate recruiter/receptor, is a key mechanism of action of the IMiDs and the CELMoD agents. Two CELMoD agents, iberdomide and mezigdomide, have demonstrated substantial preclinical and clinical activity in MM and have entered phase 3 investigation. Using a literature search methodology comprising searches of PubMed (unlimited time-frame) and international hematology/oncology conference abstracts (2019-2023), this paper reviews the importance of Ikaros and Aiolos in MM, the mechanism of action of the IMiDs and CELMoD agents and their relative potency for targeting Ikaros and Aiolos, and preclinical and clinical data on iberdomide and mezigdomide. Expert Opinion: Emerging data suggest that iberdomide and mezigdomide have promising activity, including in IMiD-resistant settings and, pending phase 3 findings, may provide additional treatment options for patients with MM. |
| فهرسة مساهمة: | Keywords: Aiolos; CELMoD agents; Ikaros; cereblon; iberdomide; mezigdomide; multiple myeloma; relapsed/refractory |
| المشرفين على المادة: | 148971-36-2 (Ikaros Transcription Factor) 4Z8R6ORS6L (Thalidomide) 0 (IKZF1 protein, human) 0 (IKZF3 protein, human) 8V66F27X44 (iberdomide) 0 (Signaling Lymphocytic Activation Molecule Family) EC 2.3.2.27 (Ubiquitin-Protein Ligases) 0 (Antineoplastic Agents) 0 (CRBN protein, human) 0 (IL17RB protein, human) 0 (SLAMF7 protein, human) 0 (Immunomodulating Agents) 0 (Piperidones) 0 (Morpholines) 0 (Receptors, Interleukin-17) 0 (Adaptor Proteins, Signal Transducing) 0 (Phthalimides) |
| تواريخ الأحداث: | Date Created: 20240726 Date Completed: 20240801 Latest Revision: 20240801 |
| رمز التحديث: | 20240801 |
| DOI: | 10.1080/17474086.2024.2382897 |
| PMID: | 39054911 |
| قاعدة البيانات: | MEDLINE |
PDF full text from Publisher | تدمد: | 1747-4094 |
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| DOI: | 10.1080/17474086.2024.2382897 |