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A Potential Role for HUWE1 in Modulating Cisplatin Sensitivity Wenmaekers, Stijn; Viergever, Bastiaan J.; Kumar, Gunjan; Kranenburg, Onno; Black, Peter C.; Daugaard, Mads; Meijer, Richard P.

Abstract

Cisplatin is a widely used antineoplastic agent, whose efficacy is limited by primary and acquired therapeutic resistance. Recently, a bladder cancer genome-wide CRISPR/Cas9 knock-out screen correlated cisplatin sensitivity to multiple genetic biomarkers. Among the screen’s top hits was the HECT domain-containing ubiquitin E3 ligase (HUWE1). In this review, HUWE1 is postulated as a therapeutic response modulator, affecting the collision between platinum-DNA adducts and the replication fork, the primary cytotoxic action of platins. HUWE1 can alter the cytotoxic response to platins by targeting essential components of the DNA damage response including BRCA1, p53, and Mcl-1. Deficiency of HUWE1 could lead to enhanced DNA damage repair and a dysfunctional apoptotic apparatus, thereby inducing resistance to platins. Future research on the relationship between HUWE1 and platins could generate new mechanistic insights into therapy resistance. Ultimately, HUWE1 might serve as a clinical biomarker to tailor cancer treatment strategies, thereby improving cancer care and patient outcomes.

Item Metadata

Title
A Potential Role for HUWE1 in Modulating Cisplatin Sensitivity
Creator
Wenmaekers, Stijn; Viergever, Bastiaan J.; Kumar, Gunjan; Kranenburg, Onno; Black, Peter C.; Daugaard, Mads; Meijer, Richard P.
Contributor
Vancouver Prostate Centre
Publisher
Multidisciplinary Digital Publishing Institute
Date Issued
2021-05-20
Description
Cisplatin is a widely used antineoplastic agent, whose efficacy is limited by primary and acquired therapeutic resistance. Recently, a bladder cancer genome-wide CRISPR/Cas9 knock-out screen correlated cisplatin sensitivity to multiple genetic biomarkers. Among the screen’s top hits was the HECT domain-containing ubiquitin E3 ligase (HUWE1). In this review, HUWE1 is postulated as a therapeutic response modulator, affecting the collision between platinum-DNA adducts and the replication fork, the primary cytotoxic action of platins. HUWE1 can alter the cytotoxic response to platins by targeting essential components of the DNA damage response including BRCA1, p53, and Mcl-1. Deficiency of HUWE1 could lead to enhanced DNA damage repair and a dysfunctional apoptotic apparatus, thereby inducing resistance to platins. Future research on the relationship between HUWE1 and platins could generate new mechanistic insights into therapy resistance. Ultimately, HUWE1 might serve as a clinical biomarker to tailor cancer treatment strategies, thereby improving cancer care and patient outcomes.
Subject
chemotherapy; resistance; biomarkers; translational medicine research; ubiquitination; DNA damage response; apoptosis
Genre
Article
Type
Text
Language
eng
Date Available
2021-05-26
Provider
Vancouver : University of British Columbia Library
Rights
CC BY 4.0
DOI
10.14288/1.0398174
URI
http://hdl.handle.net/2429/78463
Affiliation
Medicine, Faculty of; Other UBC; Non UBC; Urologic Sciences, Department of
Citation
Cells 10 (5): 1262 (2021)
Publisher DOI
10.3390/cells10051262
Peer Review Status
Reviewed
Scholarly Level
Faculty
Rights URI
https://creativecommons.org/licenses/by/4.0/
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CC BY 4.0