Regulated cell death programs shaping cancer therapy

Sep 23, 2026

Uploaded by kopisore

Regulated cell death is foundational to cancer therapy, with apoptosis historically viewed as the dominant driver of treatment benefit. Emerging evidence shows tumors can exploit multiple regulated modalities, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, and autophagy-associated death, along with stress-induced programs such as parthanatos and disulfidptosis. These pathways vary in mechanistic definition and translational readiness, and their activation or suppression reshapes tumor progression, immune signaling, and therapy resistance. Therapeutic targeting can improve control, yet death-associated signaling may also enable adaptation and immune evasion, depending on context.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages31

Reading Time1 h 18 min

AccessFree to download

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Cellular Oncology (2026) 49:102 [https://doi.org/10.1007/s13402-026-01232-3](https://doi.org/10.1007/s13402-026-01232-3) REVIEW Regulated cell death programs shaping cancer therapy Haiwen Luo1 · Yingjie Guo2 Received: 17 January 2026 / Accepted: 19 May 2026 © The Author(s) 2026 Abstract Background Regulated cell death has long been central to cancer therapy, with apoptosis historically regarded as the principal mechanism underlying treatment efficacy. Main body Increasing evidence now demonstrates that tumors engage a diverse array of regulated cell death programs, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, autophagy-associated death processes, and emerging stress-induced modalities such as parthanatos and disulfidptosis. These pathways can be broadly conceptualized as proteingoverned, metabolism-driven, or stress-induced programs, reflecting distinct mechanistic principles and differing degrees of mechanistic definition and translational maturity. Their activation or suppression can influence tumor progression, immune modulation, and therapy resistance. While therapeutic induction of specific death modalities offers opportunities for tumor control, death-associated signaling may also paradoxically promote tumor adaptation and immune evasion under certain conditions. Conclusions This review integrates current understanding of regulated cell death programs to highlight their plasticity in cancer and underscores the importance of mechanism-guided targeting of death pathways to improve cancer therapy outcomes. Clinical trial registration Not applicable. Keywords Regulated cell death · Apoptosis · Ferroptosis · Cellular stress · Therapy resistance Abbreviations 7-DHC AA ACC ACPACSL4 AdA ADAR1 ADCDAKT AMPK ASC ATG 7-dehydrocholesterol Arachidonic acid Acetyl-CoA carboxylase Acyl-carrier protein Acyl-coenzyme A synthetase long-chain family member 4 Adrenic acid Adenosine deaminase RNA specific 1 Autophagy-dependent cell death Protein kinase B AMP-activated protein kinase Apoptosis-associated speck-like protein containing a CARD Autophagy-related protein 􀀍 Yingjie Guo [yingjie.guo@arcinstitute.org](yingjie.guo@arcinstitute.org) 1 Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA 2 Arc Institute, 3181 Porter Dr, Palo Alto, CA 94304, USA BAK BAX BH2 BH4 BIM BIR CAR-T CBD CCL20 ccRCC cFLIP cGAS-STING circRNAs CLL CSCCTR1 CUL3 CYB5R1 CYLD DAMPs DBP BCL-2 antagonist/killer BCL-2-associated X protein Dihydrobiopterin Tetrahydrobiopterin BCL-2-like protein 11 Baculoviral IAP repeat Chimeric antigen receptor T cell Cannabidiol C-C motif chemokine ligand 20 Clear-cell renal cell carcinoma Cellular FLICE-inhibitory protein Cyclic GMP-AMP synthase-stimulator of interferon genes Circular RNAs Chronic lymphocytic leukemia Cancer stem cell Copper transporter-1 E3 ubiquitin ligase cullin 3 NADH-cytochrome b5 reductase Cylindromatosis Damage-associated molecular patterns Dynamic BH3 profiling DBT DD DED DepMap DHFRDHODH DISC DLAT DLST DMT1 DPP9 DTCs EMT EPAC ES ESCRT FABP7 FAO FDA FDX1 FSP1 GCH1 GCSH GLRX5 GPX4 GSDM GSH HCC HCQHIF-1α IAPs IFN-γ iPLA2 ISCU LA LDH LIASLIPT1 LIPT2 LOXs LPCAT3 LPS Lp-PLA2 LUADMCP-1 MHC-I miR MLKL Dihydrolipoyl transacylase Death domain Death effector domain Cancer Dependency Map Dihydrofolate reductase Dihydroorotate dehydrogenase Death-inducing signaling complex Dihydrolipoyl transacetylase Dihydrolipoyllysine-residuesuccinyltransferase Divalent metal transporter 1 Dipeptidyl peptidase 9 Disseminated tumor cells Epithelial-mesenchymal transitions Exchange protein directly activated by cAMP Elesclomol Endosomal sorting complexes required for transport Fatty acid-binding protein 7 Fatty acid oxidation Food and Drug Administration Ferredoxin 1 Ferroptos

FAQs

Why has apoptosis historically been considered central to cancer therapy efficacy?

Apoptosis has long been regarded as the principal mechanism underlying treatment efficacy in cancer. The review contrasts this historical view with broader regulated cell death options now recognized in tumors.

Which regulated cell death programs are discussed as important in cancer?

The review highlights apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, and autophagy-associated death processes. It also mentions emerging stress-induced modalities including parthanatos and disulfidptosis.

How can targeting regulated death pathways affect tumor outcomes and therapy resistance?

Activation or suppression of these pathways can influence tumor progression, immune modulation, and therapy resistance. Although inducing specific death modalities can support tumor control, related signaling may also promote tumor adaptation and immune evasion under certain conditions.

Sep 23, 2026

Uploaded by kopisore