Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research

Journal of Hematology & Oncology

Review

Bo Zhang¹  Jin Xu¹  Mingming Xiao¹  Si Shi¹  Xuhui Tong¹  Wei Wang¹  Jiang Liu²  Rong Tang²  Xianjun Yu² 

[1] Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 Dong’An Road, 200032, Shanghai, China;Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;Shanghai Pancreatic Cancer Institute, No. 270 Dong’An Road, 200032, Shanghai, China;Pancreatic Cancer Institute, Fudan University, Shanghai, China;

关键词: Necroptosis;    Pyroptosis;    Ferroptosis;    Cuproptosis;    Tumor microenvironment;    Nanoparticles;   

DOI  :  10.1186/s13045-022-01392-3

 received in 2022-11-22, accepted in 2022-11-30,  发布年份 2022

来源: Springer

【 摘 要 】

Many types of human cells self-destruct to maintain biological homeostasis and defend the body against pathogenic substances. This process, called regulated cell death (RCD), is important for various biological activities, including the clearance of aberrant cells. Thus, RCD pathways represented by apoptosis have increased in importance as a target for the development of cancer medications in recent years. However, because tumor cells show avoidance to apoptosis, which causes treatment resistance and recurrence, numerous studies have been devoted to alternative cancer cell mortality processes, namely necroptosis, pyroptosis, ferroptosis, and cuproptosis; these RCD modalities have been extensively studied and shown to be crucial to cancer therapy effectiveness. Furthermore, evidence suggests that tumor cells undergoing regulated death may alter the immunogenicity of the tumor microenvironment (TME) to some extent, rendering it more suitable for inhibiting cancer progression and metastasis. In addition, other types of cells and components in the TME undergo the abovementioned forms of death and induce immune attacks on tumor cells, resulting in enhanced antitumor responses. Hence, this review discusses the molecular processes and features of necroptosis, pyroptosis, ferroptosis, and cuproptosis and the effects of these novel RCD modalities on tumor cell proliferation and cancer metastasis. Importantly, it introduces the complex effects of novel forms of tumor cell death on the TME and the regulated death of other cells in the TME that affect tumor biology. It also summarizes the potential agents and nanoparticles that induce or inhibit novel RCD pathways and their therapeutic effects on cancer based on evidence from in vivo and in vitro studies and reports clinical trials in which RCD inducers have been evaluated as treatments for cancer patients. Lastly, we also summarized the impact of modulating the RCD processes on cancer drug resistance and the advantages of adding RCD modulators to cancer treatment over conventional treatments.

【 授权许可】

CC BY   
© The Author(s) 2022

【 图 表 】

Fig. 1

Fig. 5

Fig. 3

Fig. 1

Fig. 2

Fig. 1