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

Abstract

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.

Ferroptosis and Senescence: A Systematic Review

“…Tong et al, described in a review the mechanisms of necroptosis, pyroptosis, ferroptosis, and cuproptosis and the effects on tumour cell proliferation and cancer metastasis. The authors draw attention onto the potential agents and nanoparticles for cancer treatment or the association of these with already existing therapies inducing RCD compared to conventional treatments [ 50 ].…”

The prognostic and immune significance of C15orf48 in pan-cancer and its relationship with proliferation and apoptosis of thyroid carcinoma

“…These results indicate that ICB treatment may be effective for the C15orf48 high-expression group, but not the low-expression group. Pathway analysis showed that C15orf48 was significantly associated with various pathways, such as apoptosis, P53 pathway, and ferroptosis, which are critical in cancer development and immunotherapy (40,41). Subtype studies have revealed heterogeneity among the different subtypes in THCA.…”

Ferroptosis and Senescence: A Systematic Review

“…Xuhui Tong et al, described in a review the mechanisms of necroptosis, pyroptosis, ferroptosis, and cuproptosis and the effects on tumor cell proliferation and cancer metastasis. The authors draw attention to the potential agents and nanoparticles for cancer treatment or the association of these with already existing therapies inducing RCD compared to conventional treatments [55].…”