Novel targeted therapies in chronic myeloid leukemia

Muhammad Sameer Ashaq; Qian Zhou; Zhuoran Li; Baobing Zhao

doi:10.1016/j.pscia.2024.100052

Pharmaceutical Science Advances ›› 2024, Vol. 2 ›› Issue (1) : 100052 DOI: 10.1016/j.pscia.2024.100052

Review Article

research-article

Novel targeted therapies in chronic myeloid leukemia

Muhammad Sameer Ashaq ^a^,^b^,^c^,¹
, Qian Zhou ^a^,^b^,^c^,¹
, Zhuoran Li ^a^,^b^,^c
, Baobing Zhao ^a^,^b^,^c^,^*

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Abstract

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.

Keywords

Chronic myeloid leukemia / Stem cells / BCR-ABL1 / Tyrosine kinase inhibitors / Targeted therapy

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Muhammad Sameer Ashaq, Qian Zhou, Zhuoran Li, Baobing Zhao. Novel targeted therapies in chronic myeloid leukemia. Pharmaceutical Science Advances, 2024, 2(1): 100052 DOI:10.1016/j.pscia.2024.100052

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Funding

This work was supported by the National Natural Science Foundation of China (grant number 81874294); Shandong Province (grant number TSQN201812015), the Shandong University (grant number 2020QNQT007); and the Natural Science Foundation of Shandong Province (grant number ZR2022LSW027).

CRediT authorship contribution statement

Muhammad Sameer Ashaq: Writing - original draft. Qian Zhou: Writing - original draft. Zhuoran Li: Writing - original draft. Baobing Zhao: Writing - review & editing.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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