Deubiquitinases as novel therapeutic targets in colorectal cancer DOI Open Access

Noor Al Shukri,

Razik Bin Abdul Momin

Asia-Pacific Journal of Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Colorectal cancer (CRC) is one of the leading causes cancer-related mortality and third most prevalent malignant tumor in world. In recent years, key role protein post-translational modifications, especially ubiquitination deubiquitination tumorigenesis progression has gradually been revealed. Deuubiquitinating Enzymes (DUBs) play an important CRC cell proliferation, apoptosis, autophagy, immune escape, chemotherapy resistance by removing ubiquitin chains from proteins, regulating stability, activity, subcellular localization. Research shown that DUBs such as USP7, USP10, USP22 promote metastasis stabilizing associated proteins β-catenin, p53, c-Myc, activating signaling pathways Wnt/β-catenin ERK/MAPK. addition, exacerbate malignancy microenvironment (TME) inflammatory responses, polarization macrophages. Meanwhile, are closely related to resistance, decreased drug sensitivity maintaining stability targets or enhancing anti-apoptotic function. At present, small molecule inhibitors targeting have made certain progress, USP7 inhibitor P5091 USP14 IU1, providing new directions for treatment CRC. However, clinical applications still face challenges selectivity safety concerns. summary, in-depth research on molecular mechanisms CRC, development more efficient specific targeted inhibitors, exploration their combined application with other therapeutic methods expected provide strategies diagnosis

Language: Английский

Deubiquitinases as novel therapeutic targets in colorectal cancer DOI Open Access

Noor Al Shukri,

Razik Bin Abdul Momin

Asia-Pacific Journal of Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Colorectal cancer (CRC) is one of the leading causes cancer-related mortality and third most prevalent malignant tumor in world. In recent years, key role protein post-translational modifications, especially ubiquitination deubiquitination tumorigenesis progression has gradually been revealed. Deuubiquitinating Enzymes (DUBs) play an important CRC cell proliferation, apoptosis, autophagy, immune escape, chemotherapy resistance by removing ubiquitin chains from proteins, regulating stability, activity, subcellular localization. Research shown that DUBs such as USP7, USP10, USP22 promote metastasis stabilizing associated proteins β-catenin, p53, c-Myc, activating signaling pathways Wnt/β-catenin ERK/MAPK. addition, exacerbate malignancy microenvironment (TME) inflammatory responses, polarization macrophages. Meanwhile, are closely related to resistance, decreased drug sensitivity maintaining stability targets or enhancing anti-apoptotic function. At present, small molecule inhibitors targeting have made certain progress, USP7 inhibitor P5091 USP14 IU1, providing new directions for treatment CRC. However, clinical applications still face challenges selectivity safety concerns. summary, in-depth research on molecular mechanisms CRC, development more efficient specific targeted inhibitors, exploration their combined application with other therapeutic methods expected provide strategies diagnosis

Language: Английский

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