Non-apoptotic cell death-based cancer therapy:Molecular mechanism,pharmacological modulators,and nanomedicine

作     者：Xuan Wang Peng Hua Chengwei He Meiwan Chen Xuan Wang;Peng Hua;Chengwei He;Meiwan Chen

作者机构：State Key Laboratory of Quality Research in Chinese MedicineInstitute of Chinese Medical SciencesUniversity of MacaoMacaoSAR 999078China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2022年第12卷第9期

页      面：3567-3593页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China (51922111) the Science and Technology Development Fund, Macao SAR (File No. 0124/2019/A3, China) Guangdong-Hong Kong-Macao Joint Laboratory of Optoelectronic and Magnetic Functional Materials (2019B121205002, China) 

主　　题：Non-apoptotic cell death Ferroptosis Necroptosis Pyroptosis Autophagy Nanomedicine Combination therapies Anticancer 

摘      要：As an emerging cancer therapeutic target,non-apoptotic cell death such as ferroptosis,necroptosis and pyroptosis,etc.,has revealed significant potential in cancer treatment for bypassing apoptosis to enhance the undermined therapeutic efficacy triggered by apoptosis resistance.A variety of anticancer drugs,synthesized compounds and natural products have been proven recently to induce non-apoptotic cell death and exhibit excellent anti-tumor effects.Moreover,the convergence of nanotechnology with functional materials and biomedicine science has provided tremendous opportunities to construct non-apoptotic cell death-based nanomedicine for innovative cancer therapy.Nanocarriers are not only employed in targeted delivery of non-apoptotic inducers,but also used as therapeutic components to induce non-apoptotic cell death to achieve efficient tumor treatment.This review first introduces the main characteristics,the mechanism and various pharmacological modulators of different non-apoptotic cell death forms,including ferroptosis,necroptosis,pyroptosis,autophagy,paraptosis,lysosomal-dependent cell death,and oncosis.Second,we comprehensively review the latest progresses of nanomedicine that induces various forms of non-apoptotic cell death and focus on the nanomedicine targeting different pathways and components.Furthermore,the combination therapies of non-apoptotic cell death with photothermal therapy,photodynamic therapy,immunotherapy and other modalities are summarized.Finally,the challenges and future perspectives in this regard are also discussed.