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Cited by 883Cell death mechanisms and regulationFerroptosis and cancer prognosisCancer-related Molecular Pathways

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

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Tong, Xuhui, Tang, Rong, Xiao, Mingming, Xu, Jin, Wang, Wei, Zhang, Bo, Liu, Jiang, Yu, Xianjun +1 more·2022·Journal of Hematology & Oncology
DOI 10.1186/s13045-022-01392-3PMC PMC9733270
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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.

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  • Ferroptosis plays a crucial role in regulating sensitivity of tumor cells to anti-tumor therapies.

    “Ferroptosis plays a crucial role in regulating the sensitivity of tumor cells to anti-tumor therapies [48].”

    From Nanosensitizer-assisted sonodynamic therapy for breast cancer (2025) · cites this paper as [48]

  • Ferroptosis is a type of programmed cell death that differs from necrosis, apoptosis, and autophagy.

    “Ferroptosis is a type of programmed cell death that differs from common cell death patterns, such as necrosis, apoptosis, and autophagy.”

    From Nanosensitizer-assisted sonodynamic therapy for breast cancer (2025) · cites this paper as [48]

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Sorted by citations

Authors
Tong, X., Tang, R., Xiao, M., Xu, J., Wang, W., Zhang, B., Liu, J., Yu, X., & Shi, S.
Affiliations
  • Shanghai Medical College of Fudan University (CN)
  • Fudan University (CN)
Corresponding author
  • Yu, Xianjun
  • Shi, Si
ORCID
Venue
Journal of Hematology & Oncology
Publisher
Springer Science and Business Media LLC
Published
2022-12-08
Volume
15
Issue
1
Pages
174-174
ISSN
1756-8722 (ISSN-L)
DOI
10.1186/s13045-022-01392-3
PMC
PMC9733270
OpenAlex
W4311674730
Cited by
883
References
23
Citations by year
2026: 176 · 2025: 310 · 2024: 283 · 2023: 114
FWCI
18.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Hematology & Oncology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (U21A20374, 82072698, 2019-01-07-00-07-E00057, SHDC2020CR1006A, 21JC1401500, 20QA1402100, 2021011, 2019-01)
  • Shanghai Hospital Development Center (82072698, U21A20374, SHDC2020CR1006A, 2021-011, 20QA1402100, 2019-01-07-00-07-E00057, 21JC1401500)
  • Shanghai Rising-Star Program (2021-011, 20QA1402100, 21JC1401500, 82072698, SHDC2020CR1006A, 2019-01-07-00-07-E00057, U21A20374)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
regulated cell death, necroptosis, pyroptosis, ferroptosis, cuproptosis, cancer therapy, tumor microenvironment, immunogenic cell death, metastasis, chemoresistance, nanoparticles, apoptosis evasion
MeSH terms
Pyroptosis, Necroptosis, Ferroptosis, Copper, Humans, Neoplasms, Cell Death, Apoptosis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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