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Protein\u2013protein interaction, signaling, and gene regulatory networks are increasingly used to describe plasticity\u2010induced cellular adaptation in disease progression. This review delineates how network analysis of cell plasticity leads to novel therapy options against 1) cancer progression; 2) epithelial\u2013mesenchymal transition\u2010induced metastases; 3) cancer stem cells, and 4) pre\u2010existent drug\u2010resistant cells. Network plasticity\u2010designed sequential and differentiation therapies are also outlined. 55 plasticity\u2010related cancer drug targets are listed, where 20 have already approved drugs, 9 have investigational drugs, and 26 are drug target candidates. The recent expansion of plastic network\u2010driven pancreatic beta cell and neuron regeneration therapies is described in diabetes, as well as in Alzheimer's and Parkinson's diseases, respectively. Finally, six major network\u2010related research gaps and promising future research areas are outlined, including the discovery of plasticity\u2010related cancer signaling pathways and cross\u2010talks, cancer resensitization therapies, and the use of recently available proteome\u2010wide network data and models to find novel cancer cell differentiation cocktails, drug targets, proper timing, and biomarkers of sequential therapies, as well as to perform in silico drug combination screens and in silico clinical trials.<\/jats:p>","DOI":"10.1002\/advs.202522532","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T12:38:30Z","timestamp":1769863110000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Modulation of Network Plasticity Opens Novel Therapeutic Possibilities in Cancer, Diabetes, and Neurodegeneration"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1542-8304","authenticated-orcid":false,"given":"M\u00e1rk","family":"Kerest\u00e9ly","sequence":"first","affiliation":[{"name":"Department of Molecular Biology Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9834-190X","authenticated-orcid":false,"given":"Istv\u00e1n","family":"Narozsny","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0373-8543","authenticated-orcid":false,"given":"Levente","family":"Szarka","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2968-0666","authenticated-orcid":false,"given":"Daniel V.","family":"Veres","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Semmelweis University  Budapest Hungary"},{"name":"Turbine Simulated Cell Technologies  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9234-0659","authenticated-orcid":false,"given":"Peter","family":"Csermely","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2011-8316","authenticated-orcid":false,"given":"D\u00e1vid","family":"Keresztes","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,31]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal2380"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.11.011"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-0015"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-1059"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009988"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1088\/1478-3975\/ac4ee2"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01383-x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.279783.124"},{"key":"e_1_2_11_10_1","first-page":"77","article-title":"Stability\/Flexibility: The Tightly Coupled Homeostasis Generator Is at the Same Time the Driver of Change","volume":"60","author":"Giuliani A.","year":"2024","journal-title":"Ann Ist Super Sanita"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201700150"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.17102"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-54859-8"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2019.12.005"},{"key":"e_1_2_11_15_1","article-title":"Cancer Progression as a Learning Process","volume":"25","author":"Shomar A.","year":"2022","journal-title":"Science"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010285"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2024.10.041"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-025-05770-1"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-025-08411-2"},{"key":"e_1_2_11_20_1","first-page":"622","article-title":"The Developmental Capacity of Nuclei Taken From Intestinal Epithelium Cells of Feeding Tadpoles","volume":"10","author":"Gurdon J. 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