Genome-wide CRISPR/Cas9 screening for drug resistance in tumors

作者：Zhang, Zhongyan; Wang, Hailiang; Yan, Qian; Cui, Jinwei; Chen, Yubin; Ruan, Shiye; Yang, Jiayu; Wu, Zelong; Han, Mingqian; Huang, Shanzhou^*; Zhou, Qi^*; Zhang, Chuanzhao^*; Hou, Baohua^*

来源：Frontiers in Pharmacology, 2023, 14: 1284610.

DOI：10.3389/fphar.2023.1284610

• drug resistance
• tumors
• genome-wide CRISPR/Cas9 screening
• MAPK pathway inhibitors
• PARP inhibitors

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-kappa B pathway. Also, we analyze the limitations and conditions for the application of genome-wide CRISPR/Cas9 screening techniques.

• 单位
  中山大学; 南方医科大学; 1; 广东省人民医院; 青岛大学