RCDome

The Regulated Cell Death Compendium — a comprehensive, literature-verified reference of the 25 recognized forms of regulated cell death, classified by mechanism, molecular machinery, inflammatory nature, and cancer relevance. Each entry is traceable to its foundational discovery and characterization papers via verified PubMed identifiers. Designed as a canonical reference framework for multi-optosis research and clinical translation.

25 RCD Forms — Comprehensive Reference Table

All references verified against PubMed (July 2026). Primary references = foundational discovery/characterization papers. Secondary references = reviews providing molecular, mechanistic, or cancer-context support. Galluzzi et al. (2018) PMID:29362479 is the universal NCCD consensus reference for all forms.

Source: https://lbtgenomica.uenf.br/cancerrcdpredictor/

Citation: Rodrigues de Souza E., Almeida Cordeiro Nogueira H., dos Santos Lopes V. and Medina-Acosta E. (2026). A Pan-Cancer Multi-Omic SuperLearner for Regulated Cell Death Survival Topologies. bioRxiv: 2026.05.29.728842.

# RCD Form Category Core Mechanism Key Molecules Inflammatory? Cancer Relevance Primary References (PMID) Secondary References (PMID)
1 Apoptosis Executioner Programmed cell death with shrinkage, chromatin condensation, DNA fragmentation Caspases (3,8,9), BCL-2 family, cytochrome c No Evasion is a cancer hallmark; reactivation is a central therapeutic focus Elmore (2007) Toxicol Pathol 35:495–516 [17562483]; Galluzzi et al. (2018) Cell Death Differ 25:486–541 [29362479] Taylor et al. (2008) Nat Rev Mol Cell Biol 9:231–241 [18073771]
2 Necroptosis Executioner Programmed necrosis via RIPK1/RIPK3/MLKL with plasma membrane rupture RIPK1, RIPK3, MLKL Yes Dual: anti-tumor immunity vs. tumor-promoting inflammation Sun et al. (2012) Cell 148:213–227 [22265413]; Galluzzi et al. (2018) [29362479] Vanden Berghe et al. (2014) Nat Rev Mol Cell Biol 15:135–147 [24452471]; Zhang et al. (2022) Semin Cancer Biol [35908574]
3 Pyroptosis Executioner Caspase-1/gasdermin-mediated lysis Caspase-1, GSDMD, NLRP3 inflammasome Yes Anti-tumor immunity via cytokine release; can also promote progression Shi et al. (2015) Nature 526:660–665 [26375003]; Galluzzi et al. (2018) [29362479]
4 Ferroptosis Executioner Iron-dependent lipid peroxide accumulation GPX4, SLC7A11, ACSL4, iron Yes (oxidative) Eliminates high-oxidative-stress cells; targets apoptosis-resistant cancers Dixon et al. (2012) Cell 149:1060–1072 [22632970]; Stockwell et al. (2017) Cell 171:273–285 [28985560]
5 Autophagy Executioner Lysosomal self-digestion and cellular recycling ATG proteins, LC3, Beclin-1, p62/SQSTM1 Context-dependent Dual: suppresses tumor initiation; promotes survival of established tumors under stress Debnath et al. (2023) Nat Rev Mol Cell Biol 24:560–575 [36864290]; Galluzzi et al. (2018) [29362479] Mizushima et al. (2011) Annu Rev Cell Dev Biol 27:107–132 [21801009]
6 Necrosis Executioner Cell swelling, membrane rupture, release of cellular contents ATP depletion, Ca overload (accidental); RIPK1/RIPK3 (programmed) Yes Progression via inflammatory microenvironment remodeling and immune evasion Kim et al. (2019) Exp Mol Med 51:1–10 [31827074]; Galluzzi et al. (2018) [29362479] Vanden Berghe et al. (2014) Nat Rev Mol Cell Biol 15:135–147 [24452471]
7 Anoikis Executioner Apoptosis triggered by ECM detachment Integrins, BCL-2 family, FAK No Resistance enables metastasis; hallmark of metastatic competence Frisch & Francis (1994) J Cell Biol 124:619–626 [8106557]; Galluzzi et al. (2018) [29362479] Paoli et al. (2013) Biochim Biophys Acta 1833:3481–3498 [23830918]
8 Cuproptosis Executioner Copper accumulation driving mitochondrial stress FDX1, LIAS, DLAT, copper Yes (mitochondrial) Exploits copper accumulation to selectively kill cancer cells Tsvetkov et al. (2022) Science 375:1254–1261 [35298263] Zhao et al. (2024) Cell Commun Signal 22:389 [39068453]
9 NETosis Executioner Neutrophil death releasing neutrophil extracellular traps (NETs) MPO, NE, PAD4, histones Yes Can trap/kill cancer cells; also promotes inflammation and progression Brinkmann et al. (2004) Science 303:1532–1535 [15001782]; Galluzzi et al. (2018) [29362479] Ma et al. (2024) MedComm 5:e666 [39015554]
10 Entosis Executioner Cell-in-cell cannibalism; one cell engulfing and killing another Rho/ROCK, actomyosin, E-cadherin No Kills engulfed cells; may provide survival advantages to engulfing cells Overholtzer et al. (2007) Cell 131:966–979 [18045538]; Galluzzi et al. (2018) [29362479] Das et al. (2025) Adv Exp Med Biol [41004086]
11 Parthanatos Executioner PARP-1 hyperactivation causing DNA fragmentation and AIF nuclear translocation PARP-1, AIF, MIF Yes PARP inhibition triggers parthanatos in DNA-repair-deficient tumors Fatokun et al. (2014) Br J Pharmacol 171:2000–2016 [24684389]; Galluzzi et al. (2018) [29362479] Gupta et al. (2025) EXCLI J 24:457–477 [40166425]
12 Disulfidptosis Executioner SLC7A11-mediated disulfide accumulation under glucose starvation SLC7A11, NADPH, disulfide bonds Yes (stress) Emerging target for metabolic vulnerabilities under nutrient stress Liu et al. (2023) Nat Cell Biol 25:404–414 [36747082] Hemmati et al. (2026) Discov Oncol [41961425]
13 Oxeiptosis Executioner Oxidative stress-driven, KEAP1/NRF2-dependent KEAP1, NRF2, ROS Yes (oxidative) Potential relevance to oxidative-stress-targeting approaches Holze et al. (2018) Nat Cell Biol 20:735–747 [29255269]; Galluzzi et al. (2018) [29362479]
14 Paraptosis Executioner Non-apoptotic death with ER-derived cytoplasmic vacuolation ER stress, MAPK, Ca No Overcomes apoptosis resistance via ER stress induction Sperandio et al. (2000) Proc Natl Acad Sci USA 97:14376–14381 [11121041]; Galluzzi et al. (2018) [29362479] Anceschi et al. (2026) Cell Death Discov [42373592]
15 Alkaliptosis Executioner pH-dependent death under alkaline conditions; NF-kB/CA9-dependent NF-kB, CA9, IkB Yes Targets TME through pH manipulation Song et al. (2018) Gastroenterology 154:228–240 [29248440]; Chen F et al. (2023) Cell Rep 42:112131 [36640329]
16 Lysosome-dependent cell death Executioner Lysosomal permeabilization releasing cathepsins Cathepsins (B, D, L), LAMP1/2, ROS Yes Vulnerability in tumors with altered lysosomal regulation Aits & Jaattela (2013) J Cell Sci 126:1905–1912 [23720375]; Galluzzi et al. (2018) [29362479] Wang et al. (2018) Biochim Biophys Acta Rev Cancer 1870:207–227 [30316942]
17 Mitoptosis Executioner Selective elimination of damaged mitochondria (organelle-level quality control) mPTP, ROS, mitochondrial fission proteins Yes (mitochondrial) Mitochondrial quality control failure may promote progression Lyamzaev et al. (2020) Biochemistry (Mosc) 85:1484–1498 [33705288]; Galluzzi et al. (2018) [29362479]
18 Autosis Executioner Autophagy-dependent death requiring Na/K-ATPase Na/K-ATPase, Beclin-1, ATG5/7 Yes Targets resistant cells that evade other autophagic death forms Liu et al. (2013) Proc Natl Acad Sci USA 110:20364–20371 [24277826] Depierre et al. (2024) Cell Death Dis 15:429 [38796484]
19 Erebosis Executioner Novel cell death reported in gut enterocyte turnover Poorly characterized Unknown Potential relevance to gut-associated cancers and high-turnover contexts Ciesielski et al. (2022) PLoS Biol 20:e3001713 [35468130] Note: Only one paper exists; molecular characterization pending.
20 Methuosis Executioner Non-apoptotic death with macropinosome-derived vacuoles; Ras/Rac1-driven Ras, Rac1, macropinocytosis No (rupture) Targets cancers exhibiting high macropinocytosis rates Maltese & Overmeyer (2014) Am J Pathol 184:1630–1642 [24726643]; Galluzzi et al. (2018) [29362479]
21 Mitotic catastrophe Trigger Oncosuppressive sensor of aberrant mitosis and genomic instability CDK1, Cyclin B, PLK1, Aurora kinases Downstream: Apoptosis or Necrosis Fail-safe eliminating mitotically defective cells; induced by anti-mitotic therapies Castedo et al. (2004) Oncogene 23:2825–2837 [15077146]; Galluzzi et al. (2018) [29362479]
22 Mitochondrial permeability transition (MPT) Trigger Opening of mPTP causing loss of mitochondrial membrane potential Cyclophilin D, ANT, mPTP components Downstream: Necrosis or Apoptosis May expose metabolic vulnerabilities in tumors with altered mitochondrial regulation Suh et al. (2013) Front Oncol 3:143 [23483560]; Galluzzi et al. (2018) [29362479] Boyenle et al. (2022) Mitochondrion 63:47–56 [35077882]
23 Immunogenic cell death (ICD) Functional Dying cells expose/release DAMPs activating adaptive immunity CALR, HMGB1, ATP, HSP70/90 N/A (not an executioner) Potential to convert dying tumor cells into an in situ vaccine Kroemer et al. (2013) Annu Rev Immunol 31:51–72 [23157435]; Galluzzi et al. (2017) Nat Rev Immunol 17:97–111 [27748397]
24 Efferocytosis Functional Phagocytic clearance of apoptotic/dead cells preventing inflammatory leakage MERTK, AXL, TYRO3, phosphatidylserine N/A (not an executioner) Suppresses inflammation; may impair anti-tumor immunity Qiu et al. (2023) Biomed Pharmacother 167:115404 [37741255]; Galluzzi et al. (2018) [29362479] Tajbakhsh et al. (2021) Biomed Pharmacother 140:111817 [34062411]
25 Cellular senescence Functional Stable cell cycle arrest with metabolic activity; SASP secretion p53, p16, p21, SASP factors N/A (not an executioner) Tumor suppressor; accumulated senescent cells promote progression via SASP Campisi (2013) Annu Rev Physiol 75:685–705 [23140366]; Galluzzi et al. (2018) [29362479]

Summary

Category Count Range RCD Forms
Executioner 20 #1–20 Apoptosis through Methuosis
Trigger 2 #21–22 Mitotic catastrophe, MPT
Functional 3 #23–25 ICD, Efferocytosis, Cellular senescence

Note: Key molecules reflect domain consensus supported by the cited primary and secondary references. Where secondary references are blank, the primary references provide sufficient support. Erebosis (#19) has only one published paper; molecular characterization is pending. All references verified against PubMed, July 2026.