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2000
Volume 25, Issue 9
  • ISSN: 1568-0096
  • E-ISSN: 1873-5576

Abstract

Genome instability is a key driver of malignant progression in cancer and is characterized by chromoanagenesis, including spontaneous events, such as chromothripsis, chromoanasynthesis, and chromoplexy. These genome catastrophes create the heterogeneity necessary for tumor cells to adapt, evolve, and resist therapy. Ergodic anticancer therapy represents a novel strategy for targeting cancer stem cells by manipulating their genome chaos. Two approaches have been proposed: ergodynamic anticancer therapy (EDAT), which enhances genome chaos beyond a critical threshold and leads to self-destruction, and ergostatic anticancer therapy (ESAT), which suppresses chaos and limits malignant progression. This short communication explores the conceptual foundations, molecular mechanisms, and therapeutic potential of ergostatic and ergodynamic therapies in treating cancer, highlighting their role in personalized medicine.

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2025-04-25
2025-10-28

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References

  1. ZhangC.Z. LeibowitzM.L. PellmanD. Chromothripsis and beyond: Rapid genome evolution from complex chromosomal rearrangements.Genes Dev.201327232513253010.1101/gad.229559.113 24298051
     [Google Scholar]
  2. ShenM.M. Chromoplexy: A new category of complex rearrangements in the cancer genome.Cancer Cell201323556756910.1016/j.ccr.2013.04.025 23680143
     [Google Scholar]
  3. PellestorF. Chromoanagenesis: Cataclysms behind complex chromosomal rearrangements.Mol. Cytogenet.2019121610.1186/s13039‑019‑0415‑7 30805029
     [Google Scholar]
  4. RussoG. TramontanoA. IodiceI. ChiariottiL. PezoneA. Epigenome chaos: Stochastic and deterministic DNA methylation events drive cancer evolution.Cancers2021138180010.3390/cancers13081800 33918773
     [Google Scholar]
  5. MahfouzM.M. RNA-directed DNA methylation.Plant Signal. Behav.20105780681610.4161/psb.5.7.11695 20421728
     [Google Scholar]
  6. MenezoY. ClementP. ClementA. ElderK. Methylation: An ineluctable biochemical and physiological process essential to the transmission of life.Int. J. Mol. Sci.20202123931110.3390/ijms21239311 33297303
     [Google Scholar]
  7. MooreL.D. LeT. FanG. DNA methylation and its basic function.Neuropsychopharmacology2013381233810.1038/npp.2012.112 22781841
     [Google Scholar]
  8. JoH. ShimK. JeoungD. Roles of RNA methylations in cancer progression, autophagy, and anticancer drug resistance.Int. J. Mol. Sci.2023244422510.3390/ijms24044225 36835633
     [Google Scholar]
  9. ShityakovS. Perspectives on ergodic cancer therapy derived from cloning genome chaos viain vivo rhabdomyosarcoma RA-2 models: A narrative review.J. Herb. Med.202420241110.2174/0115680096319768241003060636
     [Google Scholar]
  10. KravtsovV.Iu. GuzhovaI.V. KaminskaiaE.V. Il’inskikhN.N. Vakhtin, IuB Instability of genome and metastatic potential of rat rhabdomyosarcoma Ra-2 cells.Dokl. Akad. Nauk SSSR1990310512391242 2354652
     [Google Scholar]
  11. KravtsovV.Iu. GuzhovaI.V. KaminskaiaE.V. Il’inskikhN.N. Vakhtin, IuB Clonal analysis of karyotypic instability and metastatic potential in tumor cell populations.Genetika199026915841590 2079204
     [Google Scholar]
  12. HengJ. HengH.H. Genome chaos, information creation, and cancer emergence: Searching for new frameworks on the 50th anniversary of the “war on cancer”.Genes202113110110.3390/genes13010101 35052441
     [Google Scholar]
  13. VakhtinYu.B. Genetic Theory of Cell. Populations.LeningradNauka1980
     [Google Scholar]
  14. DuttaK. KravtsovV. OleynikovaK. RuzovA. SkorbE.V. ShityakovS. Analyzing the effects of single nucleotide polymorphisms on hnrnpa2/b1 protein stability and function: Insights for anticancer therapeutic design.ACS Omega2024955485549510.1021/acsomega.3c07195 38343990
     [Google Scholar]
  15. YangL. ShiP. ZhaoG. XuJ. PengW. ZhangJ. ZhangG. WangX. DongZ. ChenF. CuiH. Targeting cancer stem cell pathways for cancer therapy.Signal Transduct. Target. Ther.202051810.1038/s41392‑020‑0110‑5 32296030
     [Google Scholar]
  16. BorlonganM.C. WangH. Profiling and targeting cancer stem cell signaling pathways for cancer therapeutics.Front. Cell Dev. Biol.202311112517410.3389/fcell.2023.1125174 37305676
     [Google Scholar]
  17. HuX. CongY. LuoH.H. WuS. ZhaoL.E. LiuQ. YangY. Cancer stem cells therapeutic target database: The first comprehensive database for therapeutic targets of cancer stem cells.Stem Cells Transl. Med.20176233133410.5966/sctm.2015‑0289 28191780
     [Google Scholar]
  18. LiuP. ErezA. NagamaniS.C.S. DharS.U. KołodziejskaK.E. DharmadhikariA.V. CooperM.L. WiszniewskaJ. ZhangF. WithersM.A. BacinoC.A. Campos-AcevedoL.D. DelgadoM.R. FreedenbergD. GarnicaA. GrebeT.A. Hernández-AlmaguerD. ImmkenL. LalaniS.R. McLeanS.D. NorthrupH. ScagliaF. StrathearnL. TrapaneP. KangS.H.L. PatelA. CheungS.W. HastingsP.J. StankiewiczP. LupskiJ.R. BiW. Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements.Cell2011146688990310.1016/j.cell.2011.07.042 21925314
     [Google Scholar]
  19. RasnicR. LinialM. Chromoanagenesis Landscape in 10,000 TCGA Patients.Cancers20211316419710.3390/cancers13164197 34439350
     [Google Scholar]
  20. PellestorF. GatinoisV. Chromoanagenesis: A piece of the macroevolution scenario.Mol. Cytogenet.2020131310.1186/s13039‑020‑0470‑0 32010222
     [Google Scholar]
  21. PellestorF. GaillardJ.B. SchneiderA. PuechbertyJ. GatinoisV. Chromoanagenesis, the mechanisms of a genomic chaos.Semin. Cell Dev. Biol.2022123909910.1016/j.semcdb.2021.01.004 33608210
     [Google Scholar]
  22. ShityakovS. KravtsovV. SkorbE.V. NosonovskyM. Ergodicity breaking and self-destruction of cancer cells by induced genome chaos.Entropy20232613710.3390/e26010037 38248163
     [Google Scholar]
  23. RagupathiA. SinghM. PerezA.M. ZhangD. Targeting the BRCA1/2 deficient cancer with PARP inhibitors: Clinical outcomes and mechanistic insights.Front. Cell Dev. Biol.202311113347210.3389/fcell.2023.1133472 37035242
     [Google Scholar]
  24. AlotaibiF. AlshammariK. AlotaibiB.A. AlsaabH. Destabilizing the genome as a therapeutic strategy to enhance response to immune checkpoint blockade: A systematic review of clinical trials evidence from solid and hematological tumors.Front. Pharmacol.202414128059110.3389/fphar.2023.1280591 38264532
     [Google Scholar]
  25. OsrodekM. WozniakM. Targeting genome stability in melanoma—A new approach to an old field.Int. J. Mol. Sci.2021227348510.3390/ijms22073485 33800547
     [Google Scholar]
  26. ShityakovS. FoersterC. In silico predictive model to determine vector-mediated transport properties for the blood–brain barrier choline transporter.Adv. Appl. Bioinform. Chem.20147233610.2147/AABC.S63749 25214795
     [Google Scholar]
  27. ShityakovS. FörsterC.Y. SkorbE. Comparative in silico analysis of CNS-active molecules targeting the blood–brain barrier choline transporter for Alzheimer’s disease therapy. In Silico Pharmacol.20241227110.1007/s40203‑024‑00245‑w 39099798
     [Google Scholar]
  28. TamaianR. PorozovY. ShityakovS. Exhaustive in silico design and screening of novel antipsychotic compounds with improved pharmacodynamics and blood-brain barrier permeation properties.J. Biomol. Struct. Dyn.20234124148491487010.1080/07391102.2023.2184179 36927517
     [Google Scholar]
  29. ShityakovS. SkorbE.V. FörsterC.Y. DandekarT. Scaffold searching of FDA and EMA-approved drugs identifies lead candidates for drug repurposing in Alzheimer’s disease.Front Chem.2021973650910.3389/fchem.2021.736509 34751244
     [Google Scholar]
  30. ShityakovS. RoewerN. FörsterC. BroscheitJ.A. In silico investigation of propofol binding sites in human serum albumin using explicit and implicit solvation models.Comput. Biol. Chem.20177019119710.1016/j.compbiolchem.2017.06.004 28917201
     [Google Scholar]
  31. ChenX. OuS. LuoJ. HeZ. JiangQ. Advancing perspectives on the off-label use of anticancer drugs: An updated classification and exploration of categories.Front. Pharmacol.202415137454910.3389/fphar.2024.1374549 38898925
     [Google Scholar]
  32. Chunarkar-PatilP. KaleemM. MishraR. RayS. AhmadA. VermaD. BhayyeS. DubeyR. SinghH. KumarS. Anticancer drug discovery based on natural products: from computational approaches to clinical studies.Biomedicines202412120110.3390/biomedicines12010201 38255306
     [Google Scholar]
  33. ShityakovS. BigdelianE. HusseinA.A. HussainM.B. TripathiY.C. KhanM.U. ShariatiM.A. Phytochemical and pharmacological attributes of piperine: A bioactive ingredient of black pepper.Eur. J. Med. Chem.201917614916110.1016/j.ejmech.2019.04.002 31103896
     [Google Scholar]
  34. UmbreitN.T. ZhangC.Z. LynchL.D. BlaineL.J. ChengA.M. TourdotR. SunL. AlmubarakH.F. JudgeK. MitchellT.J. SpektorA. PellmanD. Mechanisms generating cancer genome complexity from a single cell division error.Science20203686488eaba071210.1126/science.aba0712 32299917
     [Google Scholar]
  35. GisselssonD. PetterssonL. HöglundM. HeidenbladM. GorunovaL. WiegantJ. MertensF. Dal CinP. MitelmanF. MandahlN. Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity.Proc. Natl. Acad. Sci. USA200097105357536210.1073/pnas.090013497 10805796
     [Google Scholar]
  36. XuM. ChenZ. ZhengJ. ZhaoQ. YuanZ. Artificial intelligence-aided optical imaging for cancer theranostics.Semin. Cancer Biol.202394628010.1016/j.semcancer.2023.06.003 37302519
     [Google Scholar]
  37. MolyneauxK. LaggnerC. Brady-KalnayS.M. Artificial Intelligence-based computational screening and functional assays identify candidate small molecule antagonists of PTPmu-dependent adhesion.Int. J. Mol. Sci.2023245427410.3390/ijms24054274 36901713
     [Google Scholar]
  38. ParkerC.G. GalmozziA. WangY. CorreiaB.E. SasakiK. JoslynC.M. KimA.S. CavallaroC.L. LawrenceR.M. JohnsonS.R. NarvaizaI. SaezE. CravattB.F. Ligand and target discovery by fragment-based screening in human cells.Cell20171683527541.e2910.1016/j.cell.2016.12.029 28111073
     [Google Scholar]
  39. SchneiderP. WelinM. SvenssonB. WalseB. SchneiderG. Virtual screening and design with machine intelligence applied to Pim‐1 kinase inhibitors.Mol. Inform.2020399200010910.1002/minf.202000109 33448694
     [Google Scholar]
  40. XuQ. ShaoD. Leveraging the synergy between anti-angiogenic therapy and immune checkpoint inhibitors to treat digestive system cancers.Front. Immunol.202415148761010.3389/fimmu.2024.1487610 39691707
     [Google Scholar]
  41. QiX. ChengC. ZhangD. YuZ. MengX. Exploring the synergy between tumor microenvironment modulation and STING agonists in cancer immunotherapy.Front. Immunol.202415148834510.3389/fimmu.2024.1488345 39712021
     [Google Scholar]
  42. YuS. WangY. HeP. ShaoB. LiuF. XiangZ. YangT. ZengY. HeT. MaJ. WangX. LiuL. Effective combinations of immunotherapy and radiotherapy for cancer treatment.Front. Oncol.20221280930410.3389/fonc.2022.809304 35198442
     [Google Scholar]
  43. BreenW.G. LeventakosK. DongH. MerrellK.W. Radiation and immunotherapy: Emerging mechanisms of synergy.J. Thorac. Dis.202012117011702310.21037/jtd‑2019‑cptn‑07 33282406
     [Google Scholar]
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Ergodic Manipulation of Genome Chaos: Innovative Strategies against Malignant Progression
Curr. Cancer Drug Targets< 25, 1180 (2025); https://doi.org/10.2174/0115680096379988250415094558
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  • Article Type:     Rapid Communication
Keyword(s): apoptosis; cancer stem cells; cancer therapeutics; cell differentiation therapy; chromosomal instability; epigenetic regulation in cancer; ergodicity; genome catastrophes; Genomic instability; molecular targeted therapy; mutation; targeted therapy

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