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

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

doi:10.3389/fphar.2023.1284610

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

Front Pharmacol. 2023 Nov 21:14:1284610. doi: 10.3389/fphar.2023.1284610. eCollection 2023.

Authors

Zhongyan Zhang^#^{1

2}, Hailiang Wang^#^{1

2

3}, Qian Yan^#^{1

4}, Jinwei Cui^{1

4}, Yubin Chen^{1

4}, Shiye Ruan^{1

2}, Jiayu Yang^{1

2}, Zelong Wu^{1

2}, Mingqian Han^{1

2}, Shanzhou Huang¹, Qi Zhou^{5

6}, Chuanzhao Zhang¹, Baohua Hou^{1

2}

Affiliations

¹ Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China.
² The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
³ Department of Hepatobiliary Surgery, Weihai Central Hospital Affiliated to Qingdao University, Weihai, China.
⁴ School of Medicine, South China University of Technology, Guangzhou, China.
⁵ Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
⁶ Department of General Surgery, Hui Ya Hospital of the First Affiliated Hospital, Sun Yat-Sen University, Huizhou, Guangdong, China.

^# Contributed equally.

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.

Keywords: MAPK pathway inhibitors; PARP inhibitors; drug resistance; genome-wide CRISPR/Cas9 screening; tumors.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the National Natural Science Foundation of (China 82102961, 82072635, 82173149, and 82072637), Special Events Supported by Heyuan People’s Hospital (YNKT202202), the Science and Technology Program of Heyuan (23051017147335), Funding of Guangdong Provincial People’s Hospital (KY012021164), Basic and applied basic research funding Guangdong Province (2021A1515012441), and the Science and Technology Program of Huizhou Daya Bay (2021002).