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Updated: Aug 9, 2025

Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes
Published on: May 23, 2025
CRISPR technology: A versatile tool to model, screen, and reverse drug resistance in cancer
Shiva Shirani-Bidabadi1, Aliye Tabatabaee2, Nazita Tavazohi3
1Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan 8174673461, Iran.
Background:
Drug resistance is a serious challenge in cancer treatment that can render chemotherapy a failure. Understanding the mechanisms behind drug resistance and developing novel therapeutic approaches are cardinal steps in overcoming this issue. Clustered regularly interspaced short palindrome repeats (CRISPR) gene-editing technology has proven to be a useful tool to study cancer drug resistance mechanisms and target the responsible genes. In this review, we evaluated original research studies that used the CRISPR tool in three areas related to drug resistance, namely screening resistance-related genes, generating modified models of resistant cells and animals, and removing resistance by genetic manipulation. We reported the targeted genes, study models, and drug groups in these studies. In addition to discussing different applications of CRISPR technology in cancer drug resistance, we analyzed drug resistance mechanisms and provided examples of CRISPR's role in studying them. Although CRISPR is a powerful tool for examining drug resistance and sensitizing resistant cells to chemotherapy, more studies are required to overcome its disadvantages, such as off-target effects, immunotoxicity, and inefficient delivery of CRISPR/cas9 into the cells.
Insights
Clustered regularly interspaced short palindrome repeats (CRISPR) gene editing advances cancer drug resistance research by identifying resistance genes and creating models. CRISPR shows promise in overcoming chemotherapy resistance but requires further study to address limitations.
Area of Science:
- Oncology
- Genetics
- Biotechnology
Background:
- Drug resistance significantly challenges cancer chemotherapy efficacy.
- Understanding resistance mechanisms and developing new therapies are critical.
- CRISPR gene editing offers a powerful approach to study and target cancer drug resistance.
Approach:
- This review evaluates original research utilizing CRISPR technology for cancer drug resistance.
- Focus areas include screening resistance-related genes, generating resistant cell/animal models, and genetic manipulation to overcome resistance.
- Key findings on targeted genes, study models, and drug classes are reported.
Key Points:
- CRISPR facilitates the identification of genes contributing to drug resistance.
- CRISPR enables the creation of sophisticated models for studying resistance mechanisms.
- CRISPR-mediated genetic manipulation can potentially reverse or sensitize cells to chemotherapy.
Conclusions:
- CRISPR technology is instrumental in dissecting complex cancer drug resistance mechanisms.
- While effective, CRISPR/Cas9 faces challenges including off-target effects, immunotoxicity, and delivery efficiency.
- Further research is essential to optimize CRISPR applications for clinical cancer therapy.
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