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Gene & Protein in Disease Targeting cathepsins during cancer development

of Bcl-xL. Similarly, novel inhibitors could be screened Ethics approval and consent to participate
86
for Cts B, L, and K, all of which can cleave both pro- and
antiapoptotic proteins, potentially inhibiting extracellular Not applicable.
Cts and their ECM-modulating effects during metastasis. Consent for publication
7. Conclusion Not applicable.

Our findings indicate the presence of a complex interplay, Availability of data
as Cts can leak from the lysosome and influence cell fate
through proteolysis of BH3 proteins. The challenge does Not applicable.
not solely exist in developing anti-cathepsin therapeutics References
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approach requires further development for therapeutic doi: 10.1038/s41392-021-00778-y
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significantly impact cancer targeting at various stages. Biol. 2003;13(3):137-145.
Consequently, this therapeutic approach may lead to a doi: 10.1016/s0962-8924(03)00005-9
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pathway proteins to prevent cancer proliferation and/ Regulators of cancer progression and therapeutic response.
or chemo-resistance as well as Cts to prevent cancer Nat Rev Cancer. 2015;15(12):712-729.
invasiveness through ECM modification. In addition,
this could enable the testing of established anticancer doi: 10.1038/nrc4027
drugs, such as BH3-mimetics and Mcl-1 inhibitors, for 4. Soond SM, Kozhevnikova MV, Zamyatnin AA Jr.
the modulation of Cts activity, promoting the stabilization “Patchiness” and basic cancer research: Unravelling the
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received FDA approval among the inhibitors listed in doi: 10.1080/15384101.2019.1632639
Table 3 (approved in 2018, as per www.fda.gov.us). This 5. Uhlman A, Folkers K, Liston J, Pancholi H, Hinton A. Effects
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Acknowledgments doi: 10.1007/s12307-017-0196-7
6. Rothberg JM, Bailey KM, Wojtkowiak JW, et al. Acid-
The author would like to acknowledge Sechenov First mediated tumor proteolysis: Contribution of cysteine
Moscow State Medical University and Northeastern cathepsins. Neoplasia. 2013;15(10):1125-1137.
Agriculture University for their continual academic
support. In addition, he would like to thank Ms. Kate S. doi: 10.1593/neo.13946
Boston for critically proofreading this manuscript and for 7. Rozhin J, Sameni M, Ziegler G, Sloane BF. Pericellular pH
her continued encouragement and support throughout the affects distribution and secretion of cathepsin B in malignant
writing process of this article. cells. Cancer Res. 1994;54(24):6517-6525.
8. Soond SM, Kozhevnikova MV, Frolova AS, et al. Lost or
Funding Forgotten: The nuclear cathepsin protein isoforms in cancer.
None. Cancer Lett. 2019;462:43-50.
doi: 10.1016/j.canlet.2019.07.020
Conflict of interest
9. Jordans S, Jenko-Kokalj S, Kuhl NM, et al. Monitoring
The author declares no competing interests in this article. compartment-specific substrate cleavage by cathepsins B,
K, L, and S at physiological pH and redox conditions. BMC
Author contributions Biochem. 2009;10:23.
This is a single-authored article. doi: 10.1186/1471-2091-10-23

Volume 4 Issue 3 (2025) 8 doi: 10.36922/gpd.4768