Novel targeted therapies in chronic myeloid leukemia
Chronic myeloid leukemia (CML) is the chronic proliferation of myeloid-lineage cells in hematopoietic stem cells driven by the BCR-ABL1 fusion oncoprotein. The development of tyrosine kinase inhibitors (TKIs) has revolutionized CML treatment; however, resistance and intolerance to these drugs remain...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | Pharmaceutical Science Advances |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2773216924000187 |
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| author | Muhammad Sameer Ashaq Qian Zhou Zhuoran Li Baobing Zhao |
| author_facet | Muhammad Sameer Ashaq Qian Zhou Zhuoran Li Baobing Zhao |
| author_sort | Muhammad Sameer Ashaq |
| collection | DOAJ |
| description | Chronic myeloid leukemia (CML) is the chronic proliferation of myeloid-lineage cells in hematopoietic stem cells driven by the BCR-ABL1 fusion oncoprotein. The development of tyrosine kinase inhibitors (TKIs) has revolutionized CML treatment; however, resistance and intolerance to these drugs remain key challenges. CML stem cells (CMLSCs) are the root cause of CML relapse and resistance to TKIs. This review discusses novel targeted therapeutic options targeting CMLSCs to address the abovementioned challenges. Numerous novel TKIs, such as flumatinib, vodobatinib, and olverembatinib, have shown remarkable potential against BCR-ABL1, but few, including AT9283, MK0457, and DCC-2036, are still undergoing clinical trials. Targeting CMLSCs is a fundamental therapeutic approach for the treatment of CML progression, relapse, and TKI resistance. In this review, novel agents targeting core signaling pathways and novel molecular targets in CMLSCs are highlighted. Currently, multiple approaches, such as targeting epigenetic modifications or microRNAs and altering metabolism in leukemic cells, have shown desirable effects in treating CML. Immunotherapy, autophagy inhibitors, and protein synthesis inhibitors are novel and effective therapies for the treatment of CML. Although various therapeutic strategies have provided exceptional results in the treatment of CML, the challenges of TKI resistance and CML remission or relapse remain. Therefore, current therapeutic approaches and targeted therapies have practical and clinical implications for achieving desirable outcomes. |
| format | Article |
| id | doaj-art-f84d99512dd84b1a90409e29b82d0241 |
| institution | Kabale University |
| issn | 2773-2169 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmaceutical Science Advances |
| spelling | doaj-art-f84d99512dd84b1a90409e29b82d02412024-12-07T08:35:18ZengElsevierPharmaceutical Science Advances2773-21692024-12-012100052Novel targeted therapies in chronic myeloid leukemiaMuhammad Sameer Ashaq0Qian Zhou1Zhuoran Li2Baobing Zhao3Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; Department of Pharmacology, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, ChinaKey Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; Department of Pharmacology, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, ChinaKey Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; Department of Pharmacology, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, ChinaKey Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; Department of Pharmacology, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; Corresponding author. Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong, 250012, China.Chronic myeloid leukemia (CML) is the chronic proliferation of myeloid-lineage cells in hematopoietic stem cells driven by the BCR-ABL1 fusion oncoprotein. The development of tyrosine kinase inhibitors (TKIs) has revolutionized CML treatment; however, resistance and intolerance to these drugs remain key challenges. CML stem cells (CMLSCs) are the root cause of CML relapse and resistance to TKIs. This review discusses novel targeted therapeutic options targeting CMLSCs to address the abovementioned challenges. Numerous novel TKIs, such as flumatinib, vodobatinib, and olverembatinib, have shown remarkable potential against BCR-ABL1, but few, including AT9283, MK0457, and DCC-2036, are still undergoing clinical trials. Targeting CMLSCs is a fundamental therapeutic approach for the treatment of CML progression, relapse, and TKI resistance. In this review, novel agents targeting core signaling pathways and novel molecular targets in CMLSCs are highlighted. Currently, multiple approaches, such as targeting epigenetic modifications or microRNAs and altering metabolism in leukemic cells, have shown desirable effects in treating CML. Immunotherapy, autophagy inhibitors, and protein synthesis inhibitors are novel and effective therapies for the treatment of CML. Although various therapeutic strategies have provided exceptional results in the treatment of CML, the challenges of TKI resistance and CML remission or relapse remain. Therefore, current therapeutic approaches and targeted therapies have practical and clinical implications for achieving desirable outcomes.http://www.sciencedirect.com/science/article/pii/S2773216924000187Chronic myeloid leukemiaStem cellsBCR-ABL1Tyrosine kinase inhibitorsTargeted therapy |
| spellingShingle | Muhammad Sameer Ashaq Qian Zhou Zhuoran Li Baobing Zhao Novel targeted therapies in chronic myeloid leukemia Pharmaceutical Science Advances Chronic myeloid leukemia Stem cells BCR-ABL1 Tyrosine kinase inhibitors Targeted therapy |
| title | Novel targeted therapies in chronic myeloid leukemia |
| title_full | Novel targeted therapies in chronic myeloid leukemia |
| title_fullStr | Novel targeted therapies in chronic myeloid leukemia |
| title_full_unstemmed | Novel targeted therapies in chronic myeloid leukemia |
| title_short | Novel targeted therapies in chronic myeloid leukemia |
| title_sort | novel targeted therapies in chronic myeloid leukemia |
| topic | Chronic myeloid leukemia Stem cells BCR-ABL1 Tyrosine kinase inhibitors Targeted therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2773216924000187 |
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