Comprehensive landscape of cell death mechanisms: from molecular cross-talk to therapeutic innovation in oncology

Cell death, or programmed cellular termination, represents a fundamental biological phenomenon crucial for maintaining organismal homeostasis. Traditionally conceptualized as a passive terminal state associated with inflammatory responses and elimination of compromised cells, contemporary research h...

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Main Authors: Ke Qi, Yongping Mu, Yang Hu, Jiayi Li, Jia Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1611055/full
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author Ke Qi
Yongping Mu
Yongping Mu
Yang Hu
Jiayi Li
Jia Liu
author_facet Ke Qi
Yongping Mu
Yongping Mu
Yang Hu
Jiayi Li
Jia Liu
author_sort Ke Qi
collection DOAJ
description Cell death, or programmed cellular termination, represents a fundamental biological phenomenon crucial for maintaining organismal homeostasis. Traditionally conceptualized as a passive terminal state associated with inflammatory responses and elimination of compromised cells, contemporary research has unveiled cell death as a sophisticated regulatory network encompassing diverse modalities, including apoptosis, necrosis, autophagic cell death, and lysosomal cell death, which are classified as programmed cell death, and pyroptosis, necroptosis, and NETosis, which are classified as inflammatory cell death, have been described over the years. Recently, several novel forms of cell death, namely, mitoptosis, paraptosis, immunogenic cell death, entosis, methuosis, parthanatos, ferroptosis, autosis, alkaliptosis, oxeiptosis, cuproptosis, erebosis and disulfidptosis, have been discovered and advanced our understanding of cell death and its complexity. This synthesis examines the historical progression and defining characteristics of cellular termination pathways, with particular emphasis on their molecular regulation and pathophysiological significance. The mechanistic diversity of these processes not only reveals intricate cellular quality control systems but also provides therapeutic opportunities for neoplastic diseases. For instance, investigations into oncogenic regulators like B-cell lymphoma 2 (BCL-2) family proteins have illuminated the critical relationship between apoptotic resistance and malignant progression, catalyzing development of pro-apoptotic agents such as BH3 mimetics. Strategic integration of these targeted therapies with conventional cytotoxic regimens and immunomodulatory approaches represents a promising frontier in precision oncology, potentially enhancing therapeutic efficacy while mitigating adverse effects in cancer management.
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spelling doaj-art-25a1d427b05e41ca8d7d1f14014e7f482025-08-20T02:40:30ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-07-011310.3389/fcell.2025.16110551611055Comprehensive landscape of cell death mechanisms: from molecular cross-talk to therapeutic innovation in oncologyKe Qi0Yongping Mu1Yongping Mu2Yang Hu3Jiayi Li4Jia Liu5Inner Mongolia Medical University, Hohhot, Inner Mongolia, ChinaInner Mongolia Medical University, Hohhot, Inner Mongolia, ChinaDepartment of Clinical Laboratory, The First Hospital of Hohhot, Hohhot, Inner Mongolia, ChinaInner Mongolia Medical University, Hohhot, Inner Mongolia, ChinaInner Mongolia Medical University, Hohhot, Inner Mongolia, ChinaInner Mongolia Medical University, Hohhot, Inner Mongolia, ChinaCell death, or programmed cellular termination, represents a fundamental biological phenomenon crucial for maintaining organismal homeostasis. Traditionally conceptualized as a passive terminal state associated with inflammatory responses and elimination of compromised cells, contemporary research has unveiled cell death as a sophisticated regulatory network encompassing diverse modalities, including apoptosis, necrosis, autophagic cell death, and lysosomal cell death, which are classified as programmed cell death, and pyroptosis, necroptosis, and NETosis, which are classified as inflammatory cell death, have been described over the years. Recently, several novel forms of cell death, namely, mitoptosis, paraptosis, immunogenic cell death, entosis, methuosis, parthanatos, ferroptosis, autosis, alkaliptosis, oxeiptosis, cuproptosis, erebosis and disulfidptosis, have been discovered and advanced our understanding of cell death and its complexity. This synthesis examines the historical progression and defining characteristics of cellular termination pathways, with particular emphasis on their molecular regulation and pathophysiological significance. The mechanistic diversity of these processes not only reveals intricate cellular quality control systems but also provides therapeutic opportunities for neoplastic diseases. For instance, investigations into oncogenic regulators like B-cell lymphoma 2 (BCL-2) family proteins have illuminated the critical relationship between apoptotic resistance and malignant progression, catalyzing development of pro-apoptotic agents such as BH3 mimetics. Strategic integration of these targeted therapies with conventional cytotoxic regimens and immunomodulatory approaches represents a promising frontier in precision oncology, potentially enhancing therapeutic efficacy while mitigating adverse effects in cancer management.https://www.frontiersin.org/articles/10.3389/fcell.2025.1611055/fullcell deathPCDcancermechanismtherapy
spellingShingle Ke Qi
Yongping Mu
Yongping Mu
Yang Hu
Jiayi Li
Jia Liu
Comprehensive landscape of cell death mechanisms: from molecular cross-talk to therapeutic innovation in oncology
Frontiers in Cell and Developmental Biology
cell death
PCD
cancer
mechanism
therapy
title Comprehensive landscape of cell death mechanisms: from molecular cross-talk to therapeutic innovation in oncology
title_full Comprehensive landscape of cell death mechanisms: from molecular cross-talk to therapeutic innovation in oncology
title_fullStr Comprehensive landscape of cell death mechanisms: from molecular cross-talk to therapeutic innovation in oncology
title_full_unstemmed Comprehensive landscape of cell death mechanisms: from molecular cross-talk to therapeutic innovation in oncology
title_short Comprehensive landscape of cell death mechanisms: from molecular cross-talk to therapeutic innovation in oncology
title_sort comprehensive landscape of cell death mechanisms from molecular cross talk to therapeutic innovation in oncology
topic cell death
PCD
cancer
mechanism
therapy
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1611055/full
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AT yanghu comprehensivelandscapeofcelldeathmechanismsfrommolecularcrosstalktotherapeuticinnovationinoncology
AT jiayili comprehensivelandscapeofcelldeathmechanismsfrommolecularcrosstalktotherapeuticinnovationinoncology
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