Several tyrosine kinase inhibitors (TKIs) have been developed as targeted therapies to inhibit the oncogenic activity of several tyrosine kinases in chronic myeloid leukemia (CML), acute lymphoid leukemia (ALL), gastrointestinal stromal tumor (GIST), and other diseases. TKIs have significantly improved the overall survival of these patients and changed the treatment strategy in the clinic. However, approximately 50% of patients develop resistance or intolerance to imatinib. For second-generation TKIs, approximately 30%-40% of patients need to change therapy by 5 years when they are used as first-line treatment. Clinical study analysis showed that the T315I mutation is highly associated with TKI resistance. Developing new drugs that target the T315I mutation will address the dilemma of treatment failure. Olverembatinib, as a third-generation TKI designed for the T315I mutation, is being researched in China. Preliminary clinical data show the safety and efficacy in treating CML patients harboring the T315I mutation or who are resistant to first- or second-line TKI treatment. Herein, we review the characteristics and clinical trials of olverembatinib. We also discuss its role in the management of CML patients.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9772831 | PMC |
| http://dx.doi.org/10.3389/fonc.2022.1036437 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
T315I - a gatekeeper point mutation and its impact on the prognosis of chronic myeloid leukemia.
Adv Lab Med
December 2024
Department of Clinical Haematology, National Institute of Blood Disease and Bone Marrow Transplantation, Karachi, Pakistan.
Objectives: kinase domain mutations are an important cause of resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukaemia (CML) of which T315I is the most treatment-resilient. This study aimed to observe the frequency of T315I and its impact on disease prognosis in terms of progression and survival.
Methods: Patients with a response which categorized them into warning zone/or who failed to respond to their TKI treatment completely as per the European LeukemiaNet (ELN) were labeled as non-responders.
Fungal secondary metabolites as a potential inhibitor of T315I- BCR::ABL1 mutant in chronic myeloid leukemia by molecular docking, molecular dynamics simulation and binding free energy exploration approaches.
J Genet Eng Biotechnol
December 2024
Hematologic Disease Center, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Medical University, Urumqi 830011, China. Electronic address:
Background: Chronic Myeloid Leukemia (CML) is particularly challenging to treat due to the T315I BCR::ABL1 mutation. Although fungal metabolites are known for their pharmaceutical potential, none are approved for CML. Our study screened approximately 2000 fungal secondary metabolites to discover inhibitors targeting the T315I- BCR::ABL1 mutant protein.
View Article and Find Full Text PDFPonatinib vs. asciminib in post-second-generation tyrosine kinase inhibitor therapy for chronic-phase chronic myeloid leukemia: a matching-adjusted indirect comparison.
Front Oncol
November 2024
Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Article Synopsis
- Ponatinib and asciminib are both approved for treating chronic-phase chronic myeloid leukemia (CP-CML) in the U.S., specifically for patients who have not responded to other therapies or have the T315I mutation, with ponatinib also available in Europe for this mutation.
- A systematic review identified clinical trials comparing the effectiveness of ponatinib and asciminib for patients who have relapsed or are resistant to treatments, and a statistical analysis was used to compare their response rates after matching patient characteristics.
- Results showed ponatinib had significantly higher response rates than asciminib, particularly in patients with the T315I mutation, indicating that ponatinib may be a more effective treatment option in these cases.
Critical role of protein kinase CK2 in chronic myeloid leukemia cells harboring the T315I BCR::ABL1 mutation.
Int J Biol Macromol
January 2025
Dept. Biomedical Sciences, University of Padova, Padova, Italy. Electronic address:
Chronic myeloid leukemia (CML) is characterized by the fusion protein BCR::ABL1, a constitutively active tyrosine kinase. The frontline treatment, represented by tyrosine kinase inhibitors (TKIs), has dramatically improved the clinical outcomes of patients. However, TKI resistance through various mechanisms has been reported.
View Article and Find Full Text PDFThe TOPASE study was set up to evaluate the outcomes of chronic myeloid leukaemia [CML] patients treated with ponatinib (PON) in a real-world setting in France. One hundred and twenty CML patients, 105 in chronic phase (CP), 8 in accelerated phase (AP) and 7 in blastic phase (BP) were included. Fifty-one (49%) of the CP-CML patients were in third line of treatment.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!