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Updated: Jul 8, 2025
Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes
Published on: May 23, 2025
Genome-wide CRISPR/Cas9 screening for drug resistance in tumors
Zhongyan Zhang1,2, Hailiang Wang1,2,3, Qian Yan1,4
1Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China.
Abstract:
Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated nuclease 9 (Cas9) screening is a simple screening method for locating loci under specific conditions, and it has been utilized in tumor drug resistance research for finding potential drug resistance-associated genes. This screening strategy has significant implications for further treatment of malignancies with acquired drug resistance. In recent years, studies involving genome-wide CRISPR/Cas9 screening have gradually increased. Here we review the recent application of genome-wide CRISPR/Cas9 screening for drug resistance, involving mitogen-activated protein kinase (MAPK) pathway inhibitors, poly (ADP-ribose) polymerase inhibitors (PARPi), alkylating agents, mitotic inhibitors, antimetabolites, immune checkpoint inhibitors (ICIs), and cyclin-dependent kinase inhibitors (CDKI). We summarize drug resistance pathways such as the KEAP1/Nrf2 pathway MAPK pathway, and NF-κB pathway. Also, we analyze the limitations and conditions for the application of genome-wide CRISPR/Cas9 screening techniques.
Insights
Genome-wide CRISPR/Cas9 screening identifies genes linked to cancer drug resistance. This powerful tool aids in understanding and overcoming treatment challenges in malignancies.
Area of Science:
- Genomics
- Cancer Biology
- Drug Discovery
Background:
- Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated nuclease 9 (Cas9) screening is a valuable method for identifying genes associated with specific cellular conditions.
- Its application in tumor drug resistance research is crucial for understanding and potentially overcoming acquired resistance in malignancies.
- The utilization of CRISPR/Cas9 screening in this field has seen a significant increase in recent years.
Purpose of the Study:
- To review the recent applications of genome-wide CRISPR/Cas9 screening in the context of cancer drug resistance.
- To summarize key drug resistance pathways and the role of CRISPR/Cas9 screening in their elucidation.
- To analyze the limitations and optimal conditions for employing genome-wide CRISPR/Cas9 screening techniques.
Main Methods:
- Review of recent literature on genome-wide CRISPR/Cas9 screening studies focused on drug resistance.
- Analysis of screening applications across various cancer therapies including mitogen-activated protein kinase (MAPK) pathway inhibitors, poly (ADP-ribose) polymerase inhibitors (PARPi), alkylating agents, mitotic inhibitors, antimetabolites, immune checkpoint inhibitors (ICIs), and cyclin-dependent kinase inhibitors (CDKIs).
- Summary of identified drug resistance pathways such as KEAP1/Nrf2, MAPK, and NF-κB pathways.
Main Results:
- Genome-wide CRISPR/Cas9 screening has been successfully applied to identify genes contributing to resistance against diverse cancer drugs.
- The technique has elucidated critical resistance mechanisms involving pathways like MAPK, KEAP1/Nrf2, and NF-κB.
- Studies highlight the potential of CRISPR/Cas9 screening to uncover novel therapeutic targets for overcoming drug resistance.
Conclusions:
- Genome-wide CRISPR/Cas9 screening is a powerful and increasingly utilized technology for dissecting cancer drug resistance mechanisms.
- This approach offers significant implications for developing strategies to treat malignancies with acquired drug resistance.
- Further research and careful consideration of limitations are essential for maximizing the utility of CRISPR/Cas9 screening in clinical oncology.
