Purinergic signalling in cancer therapeutic resistance: From mechanisms to targeting strategies

Wenhui Jia; Zhao Huang; Li Zhou; Yih-Cherng Liou; Francesco Di Virgilio; Henning Ulrich; Peter Illes; Wei Zhang; Canhua Huang; Yong Tang

doi:10.1016/j.drup.2023.100988

Purinergic signalling in cancer therapeutic resistance: From mechanisms to targeting strategies

Drug Resist Updat. 2023 Sep:70:100988. doi: 10.1016/j.drup.2023.100988. Epub 2023 Jun 28.

Authors

Wenhui Jia¹, Zhao Huang¹, Li Zhou², Yih-Cherng Liou³, Francesco Di Virgilio⁴, Henning Ulrich⁵, Peter Illes⁶, Wei Zhang⁷, Canhua Huang⁸, Yong Tang⁹

Affiliations

¹ Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
² Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
³ NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117573, Singapore; Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, Singapore 117573, Singapore.
⁴ Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
⁵ International Joint Research Centre on Purinergic Signalling, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China; Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.
⁶ International Joint Research Centre on Purinergic Signalling, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China; Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Universitaet Leipzig, Leipzig, Germany.
⁷ Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China; West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu 610041, China.
⁸ Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China; Institute of TCM-Based Stress Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. Electronic address: hcanhua@scu.edu.cn.
⁹ International Joint Research Centre on Purinergic Signalling, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China; School of Health and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China; Acupuncture and Chronobiology Key Laboratory of Sichuan Province, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China. Electronic address: tangyong@cdutcm.edu.cn.

PMID: 37413937
DOI: 10.1016/j.drup.2023.100988

Abstract

Purinergic signalling, consisting of extracellular purines and purinergic receptors, modulates cell proliferation, invasion and immunological reaction during cancer progression. Here, we focus on current evidence that suggests the crucial role of purinergic signalling in mediating cancer therapeutic resistance, the major obstacle in cancer treatment. Mechanistically, purinergic signalling can modulate the tumor microenvironment (TME), epithelial-mesenchymal transition (EMT) and anti-tumor immunity, thus affecting drug sensitivity of tumor cells. Currently, some agents attempting to target purinergic signalling either in tumor cells or in tumor-associated immune cells are under preclinical or clinical investigation. Moreover, nano-based delivery technologies significantly improve the efficacy of agents targeting purinergic signalling. In this review article, we summarize the mechanisms of purinergic signalling in promoting cancer therapeutic resistance and discuss the potentials and challenges of targeting purinergic signalling in future cancer treatment.

Keywords: Cancer; Purinergic signalling; Targeted therapy; Therapeutic resistance.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Cell Proliferation
Drug Resistance, Neoplasm*
Epithelial-Mesenchymal Transition
Humans
Neoplasms* / drug therapy
Neoplasms* / pathology
Signal Transduction
Tumor Microenvironment