[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-349508-105":59,"doc-detail-349508-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","cancer-as-an-evolutionary-reversal-time-for-a-paradigm-shift","Cancer as an evolutionary reversal - time for a paradigm shift","","Editorial commentary arguing that the somatic mutation theory cannot fully explain observed cancer behavior. It highlights discrepancies such as cancer cells reversing their phenotype in embryonic environments despite identical nuclear mutations, the tumor-suppressing role of healthy mitochondria, rare spontaneous tumor remission without treatment, and shifts in gene expression toward normal tissue. The commentary proposes that cellular phenotype is determined by gene regulatory networks and the global epigenetic state space, not single mutations.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/cancer-as-an-evolutionary-reversal-time-for-a-paradigm-shift/349508/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/cancer-as-an-evolutionary-reversal-time-for-a-paradigm-shift/349508.png","ImageObject",300,407,{"name":92,"@type":93},"kopisore","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why is the somatic mutation theory considered inconsistent with some experimental findings?","Question",{"text":113,"@type":114},"The commentary notes multiple observations where cancer behavior does not align with nuclear mutation presence or persistence, indicating that irreversible genetic changes may not be the sole drivers in all contexts.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What role do mitochondria play according to the article?",{"text":118,"@type":114},"Healthy mitochondria are described as having a tumor-suppressing effect, with cancer behavior depending on factors beyond the nuclear mutational landscape.",{"name":120,"@type":111,"acceptedAnswer":121},"How does the article explain cancer phenotype using epigenetic state space?",{"text":122,"@type":114},"It argues that phenotype depends on the collective gene expression levels and their interactions within a high-dimensional regulatory network, where distinct attractor regions correspond to different cellular states.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},349508,1790336813,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":34,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},962090880963,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Editorial Commentary  \nCancer as an evolutionary reversal—time for a paradigm shift  \nRainer J. Klement1,2^  \n1Department of Radiotherapy and Radiation Oncology, Leopoldina Hospital Schweinfurt, Schweinfurt, Germany; 2SaluGena | Praxis fürevolutionäre Naturheilkunde, Wipfeld, Germany  \nCorrespondence to: Priv.-Doz. Dr. rer. nat. Rainer J. Klement, PhD. Department of Radiotherapy and Radiation Oncology, Leopoldina Hospital Schweinfurt, Robert-Koch-Straße 10, Schweinfurt 97422, Germany; SaluGena | Praxis für evolutionäre Naturheilkunde, Wipfeld, Germany. Email: [rainer_klement@gmx.de](rainer_klement@gmx.de).  \nKeywords: Epigenetic landscape; mitochondria; state space; unicellular attractor; Waddington landscape  \nReceived: 16 February 2026; Accepted: 12 May 2026; Published online: 29 June 2026.  \ndoi: 10.21037/tbcr-2026-1-0012  \nView this article at: [https://dx.doi.org/10.21037/tbcr-2026-1-0012](https://dx.doi.org/10.21037/tbcr-2026-1-0012)  \nIntroduction  \nThe currently prevailing theory of the origin and development of cancer is the somatic mutation theory (SMT) . According to the SMT, cancer arises from the accumulation of critical gain-of-function mutations in oncogenes and/or loss-of-function mutations in tumor suppressor genes that are an inevitable feature of ageing and the interaction of our cells with the environment (e. g. , ionizing radiation and carcinogens) . As these mutations occur more or less stochastically across the nuclear genome and most mutations are neutral (passenger mutations), the emergence of cancer within the SMT has a probabilistic account of causation to it. However, the SMTis inconsistent with many experimental findings of which I will briefly list just a few. Firstly, many cancer cells brought into an embryonic environment stop behaving like cancer cells despite having the same mutations in their nuclear genome (1) . Second, similar findings have been made for cancer cells in which the cytosol has been replaced by the cytosol from healthy normal cells, but the nucleus was left intact (2) . This is evidence for a tumor-suppressing effect of healthy mitochondria regardless of the mutational landscape of nuclear DNA. Third, spontaneous remission of tumorsin cancer patients without any treatment is a phenomenon that is rare, but real and contradicts the ultimate role of (irreversible) genetic mutations as drivers of cancer (3) . Finally, tumor gene expression profiles could apparently be  \nshifted towards those of normal tissue through the intention of gifted human healers and their “biofields”(4) . To integrate these findings with the presence of cancer-characteristic mutations, it is necessary to look beyond the presence of particular oncogenic mutations and to consider the complete network of genes and their expression that can depend on external influences such as those described above.  \nThe totality of gene expression, not individual mutations, determines the cellular phenotype  \nThe phenotype of a cell is not so much determined by individual genes, but by the expression of all genes and their interactions within the gene regulatory network. The latter can be conceptualized mathematically as a highdimensional state space spanned by the expression levels of individual genes (5) . Each dimension of the state space thus corresponds to the expression level of a single gene, and at any given time, a cell occupies one point in this space determined by the expression levels of all of its genes. The interactions between these genes constrain the possible trajectories that a cell can follow within this state space overtime. Distinct cellular phenotypes correspond to distinct attractor regions within the state space, which are separated by inaccessible and mostly instable regions. Figure 1 shows a simple example for a two-gene network. Here, gene A (x-axis) inhibits the expression of gene B (y-axis) and viceversa. For this system, the x-y plane defines the state space.  \n^ ORCID: 0000-0003-1401-4270.  \n©","cbCaim2CCxR0g7ll","https://ap.wps.com/l/cbCaim2CCxR0g7ll","pdf",559627,"English","# Introduction\n## The phenotype of a cell is not so much determined by individual genes\n## The gene regulatory network as a state space\n## Epigenetic or “Waddington-like” landscape (Figure 1)","[{\"question\":\"Why is the somatic mutation theory considered inconsistent with some experimental findings?\",\"answer\":\"The commentary notes multiple observations where cancer behavior does not align with nuclear mutation presence or persistence, indicating that irreversible genetic changes may not be the sole drivers in all contexts.\"},{\"question\":\"What role do mitochondria play according to the article?\",\"answer\":\"Healthy mitochondria are described as having a tumor-suppressing effect, with cancer behavior depending on factors beyond the nuclear mutational landscape.\"},{\"question\":\"How does the article explain cancer phenotype using epigenetic state space?\",\"answer\":\"It argues that phenotype depends on the collective gene expression levels and their interactions within a high-dimensional regulatory network, where distinct attractor regions correspond to different cellular states.\"}]","Cancer as an evolutionary reversal - time for a paradigm shift | PDF",1790084001,18]