TY - JOUR

T1 - CRISPR–Cas9 potential for identifying novel therapeutic targets in muscle-invasive bladder cancer

AU - Smith, Danielle

AU - Lunj, Sapna

AU - Adamson, Anthony

AU - Nagarajan, Sankari

AU - Smith, Tim

AU - Reeves, Kim

AU - Hoskin, Peter

AU - Choudhury, Ananya

PY - 2024/7/1

Y1 - 2024/7/1

N2 - Gene editing technologies help identify the genetic perturbationsdriving tumour initiation, growth, metastasis and resistance totherapeutics. This wealth of information highlights tumour complexityand is driving cancer research towards precision medicine approachesbased on an individual’s tumour genetics. Bladder cancer is the11th most common cancer in the UK, with high rates of relapse andlow survival rates in patients with muscle-invasive bladder cancer(MIBC). MIBC is highly heterogeneous and encompasses multiplemolecular subtypes, each with diferent responses to therapeutics.This evidence highlights the need to identify innovative therapeutictargets to address the challenges posed by this heterogeneity. CRISPR–Cas9 technologies have been used to advance our understanding ofMIBC and determine novel drug targets through the identifcationof drug resistance mechanisms, targetable cell-cycle regulators, andnovel tumour suppressor and oncogenes. However, the use of thesetechnologies in the clinic remains a substantial challenge and willrequire careful consideration of dosage, safety and ethics. CRISPR–Cas9 ofers considerable potential for revolutionizing bladder cancertherapies, but substantial research is required for validation beforethese technologies can be used in the clinical setting.

AB - Gene editing technologies help identify the genetic perturbationsdriving tumour initiation, growth, metastasis and resistance totherapeutics. This wealth of information highlights tumour complexityand is driving cancer research towards precision medicine approachesbased on an individual’s tumour genetics. Bladder cancer is the11th most common cancer in the UK, with high rates of relapse andlow survival rates in patients with muscle-invasive bladder cancer(MIBC). MIBC is highly heterogeneous and encompasses multiplemolecular subtypes, each with diferent responses to therapeutics.This evidence highlights the need to identify innovative therapeutictargets to address the challenges posed by this heterogeneity. CRISPR–Cas9 technologies have been used to advance our understanding ofMIBC and determine novel drug targets through the identifcationof drug resistance mechanisms, targetable cell-cycle regulators, andnovel tumour suppressor and oncogenes. However, the use of thesetechnologies in the clinic remains a substantial challenge and willrequire careful consideration of dosage, safety and ethics. CRISPR–Cas9 ofers considerable potential for revolutionizing bladder cancertherapies, but substantial research is required for validation beforethese technologies can be used in the clinical setting.

U2 - 10.1038/s41585-024-00901-y

DO - 10.1038/s41585-024-00901-y

M3 - Review article

VL - 21

SP - 1

EP - 11

JO - Nature Reviews Urology

JF - Nature Reviews Urology

SN - 1759-4820

ER -