Affiliation:
1. Queens Centre for Oncology and Haematology Castle Hill Hospital Hull University NHS Trust Hull UK
2. Alfred Hospital Melbourne Victoria Australia
3. Centre of Biomedicine Hull York Medical School University of Hull Hull UK
4. Department of Hematology Hadassah Hebrew University Medical Center Jerusalem Israel
Abstract
AbstractIn the modern era of Chronic Lymphocytic Leukemia (CLL) targeted therapy, the loss of p53 function due to genetic abnormalities remains a significant challenge. This is because even targeted agents, which are currently the mainstay of treatment for CLL, do not directly target p53 or restore its disrupted pathway. Consequently, resistance to therapy and unfavorable clinical outcomes often accompany these p53‐related abnormalities. An essential goal of future clinical research should be to address the ostensibly “undruggable” p53 pathway. Currently, multiple therapeutic approaches are being explored to tackle TP53 dysfunction and improve outcomes in high‐risk CLL. These approaches include the use of oncoprotein murine double minute 2 inhibitors, small‐molecule p53 reactivators, exportin 1 (XPO1) inhibitors, and ataxia‐telangiectasia mutated and Rad3‐related (ATR) inhibitors. Combinations of these p53‐targeting strategies, along with established novel therapies such as B‐cell receptor or B‐cell lymphoma‐2 (BCL‐2) inhibitors, may shape the future of therapeutic trials in this challenging‐to‐treat disease.
Subject
Cancer Research,Oncology,Hematology,General Medicine
Cited by
1 articles.
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