Page 17 - TD-4-3

Tumor Discovery FBXW7 in Leukemia

regulates the degradation of several oncogenic of precision medicine has enabled the development of
proteins, including c-Myc, Notch, and cyclin E, and individualized therapeutic strategies based on a patient’s
mutations in FBXW7 can lead to the accumulation specific FBXW7 mutational landscape or functional status.
of these substrates, which, in turn, alters the tumor By integrating molecular diagnostic data, clinicians can
cell’s response to various treatments. For example, select more targeted drug regimens, thereby enhancing
the accumulation of c-Myc may increase tumor cell treatment efficacy while minimizing off-target toxicity.
sensitivity to certain chemotherapy drugs, while Concurrently, the development of therapeutics targeting
119
the stabilization of MCL-1 could enable leukemia FBXW7-associated signaling networks is actively
cells to evade apoptosis and develop chemotherapy progressing, with several candidate compounds already
resistance. By monitoring FBXW7 mutations and in preclinical or early clinical stages. Looking ahead, the
120
the accumulation of its substrates, clinicians can integration of these emerging therapeutic modalities
better predict how patients will respond to specific with patient-specific genomic profiling is expected to
treatment regimens, enabling the development of substantially improve the precision and effectiveness of
more targeted therapeutic strategies. Biomarkers leukemia treatment, ultimately contributing to enhanced
based on the FBXW7 mutation spectrum or substrate long-term survival and clinical outcomes.
accumulation can help identify patients most likely to
benefit from particular treatments, including targeted Acknowledgments
inhibitors or combination therapies. Moreover, the None.
advancement of liquid biopsy techniques, such as
121
circulating tumor DNA analysis, offers the ability Funding
to monitor FBXW7 mutations in real-time, further
facilitating personalized treatment approaches. This work was supported by the National Natural Science
This technology allows for the dynamic tracking of Foundation of China (82273167), Jiangsu Province
tumor genomic changes during treatment, providing Basic Research Program Natural Science Foundation
crucial information for optimizing therapeutic plans, (Outstanding Youth Fund Project, BK20220063), and the
adjusting drug dosages, and monitoring recurrence. Key Program of Basic Science (Natural Science) of Jiangsu
Province (22KJA350001).
6. Conclusion
Conflict of interest
FBXW7 plays a pivotal role in regulating cell cycle
progression, apoptosis, and signal transduction by targeting The authors declare no conflicts of interest.
key oncogenic proteins involved in these processes for Author contributions
ubiquitin-mediated proteasomal degradation. In leukemia,
loss or mutation of FBXW7 leads to the accumulation Conceptualization: All authors
of substrates such as c-Myc, Notch, and MCL-1, which Visualization: Xiuming Li
not only drive leukemogenesis but also contribute to Writing–original draft: All authors
therapeutic resistance. Although directly targeting FBXW7 Writing–review & editing: Bin Liu
or restoring its function remains technically challenging,
alternative therapeutic strategies aimed at inhibiting its Ethics approval and consent to participate
downstream effectors or compensating for its loss have Not applicable.
shown promising potential. For instance, synthetic lethality
approaches offer novel therapeutic avenues for FBXW7- Consent for publication
deficient malignancies. Following FBXW7 inactivation, Not applicable.
leukemia cells often become reliant on compensatory
survival pathways – such as the mTOR signaling axis – Availability of data
making them selectively vulnerable to mTOR inhibitors
without affecting normal cells. Furthermore, advances in Not applicable.
gene therapy and gene editing technologies, particularly References
CRISPR-Cas9, provide a theoretical and technical
framework for correcting FBXW7 mutations. This holds 1. Zhang A, Liu W, Qiu S. Mitochondrial genetic variations
the potential to restore its ubiquitination function, thereby in leukemia: A comprehensive overview. Blood Sci.
re-establishing the balance of cell proliferation and 2024;6(4):e00205.
differentiation. In addition, the growing implementation doi: 10.1097/BS9.0000000000000205

Volume 4 Issue 3 (2025) 9 doi: 10.36922/TD025150027