{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:36:42Z","timestamp":1791851802981,"version":"4.3.4"},"reference-count":132,"publisher":"American Society for Clinical Investigation","issue":"9","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R21CA277418"],"award-info":[{"award-number":["R21CA277418"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:p>Chemotherapy-induced alopecia (CIA) remains one of the most distressing adverse effects of cancer therapy. Yet, no therapy is available to selectively protect healthy hair follicles (HFs) and their epithelial stem cells (eHFSCs) from chemotherapy-induced damage without awarding potential survival benefits to cancer cells. Here, we report how human HFs can be protected against 2 lead CIA-inducing chemotherapeutics by inducing selective transient cell cycle arrest. Pretreating scalp HFs before chemotherapy exposure ex vivo with ALRN-6924, a clinical-stage \u201cstapled peptide\u201d drug that binds with high affinity to key endogenous inhibitors of p53, selectively activated p53 signaling only in cells with wild-type TP53 genotype and upregulated p21. This led to temporary cell cycle arrest in healthy tissues without protecting TP53-mutant cancer cells and mitigated chemotherapy-induced HF damage on multiple levels, including excessive hair matrix apoptosis, premature catagen, pigmentary abnormalities, \u201cmitotic catastrophe,\u201d and micronucleation. It also protected eHFSCs against DNA damage, apoptosis, and pathological epithelial-mesenchymal transition. Notably, even topically applied ALRN-6924 afforded relative chemotherapy protection ex vivo. These results provide proof of principle for a strategy to selectively protect rapidly proliferating healthy epithelial tissues and their stem cells in patients with TP53-mutant cancers, which promises to protect against acute and permanent CIA.<\/jats:p>","DOI":"10.1172\/jci174447","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T18:00:58Z","timestamp":1777572058000},"source":"Crossref","is-referenced-by-count":2,"title":["Transient p53\/p21 activation selectively protects healthy human hair follicles and their stem cells from chemotherapy"],"prefix":"10.1172","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4811-8580","authenticated-orcid":true,"given":"Jennifer","family":"Gherardini","sequence":"first","affiliation":[{"name":"CUTANEON \u2013 Skin & Hair Innovations, Hamburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Samra","sequence":"additional","affiliation":[{"name":"Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Gomez-Gomez","sequence":"additional","affiliation":[{"name":"Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysun","family":"Akhundlu","sequence":"additional","affiliation":[{"name":"Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha D.","family":"Verling","sequence":"additional","affiliation":[{"name":"Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinga","family":"Linowiecka","sequence":"additional","affiliation":[{"name":"CUTANEON \u2013 Skin & Hair Innovations, Hamburg, Germany."},{"name":"Department of Human Biology, Nicolaus Copernicus University, Toru\u0144, Poland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6307-7986","authenticated-orcid":true,"given":"Tongyu C.","family":"Wikramanayake","sequence":"additional","affiliation":[{"name":"Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Knie","sequence":"additional","affiliation":[{"name":"CUTANEON \u2013 Skin & Hair Innovations, Hamburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Rodr\u00edguez-Feliz","sequence":"additional","affiliation":[{"name":"Jose Rodr\u00edguez-Feliz, MD, Sol\u00e9stica Plastic Surgery & MedSpa, Coral Gables, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramtin","family":"Kassir","sequence":"additional","affiliation":[{"name":"Kassir Plastic Surgery, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Funk","sequence":"additional","affiliation":[{"name":"Sch\u00f6nheitsklinik Dr Funk M\u00fcnchen, Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza P.","family":"Azar","sequence":"additional","affiliation":[{"name":"Zentrum f\u00fcr Moderne Haartransplantation Berlin, Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3953-4590","authenticated-orcid":true,"given":"D. Allen","family":"Annis","sequence":"additional","affiliation":[{"name":"Aileron Therapeutics, Inc., Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Aivado","sequence":"additional","affiliation":[{"name":"Aileron Therapeutics, Inc., Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1901-0551","authenticated-orcid":true,"given":"J\u00e9r\u00e9my","family":"Ch\u00e9ret","sequence":"additional","affiliation":[{"name":"CUTANEON \u2013 Skin & Hair Innovations, Hamburg, Germany."},{"name":"Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Paus","sequence":"additional","affiliation":[{"name":"CUTANEON \u2013 Skin & Hair Innovations, Hamburg, Germany."},{"name":"Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/pon.3531"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2017-0263"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-023-07704-8"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70553-3"},{"issue":"4","key":"B5","first-page":"719","article-title":"Chemotherapy-induced alopecia in mice. Induction by cyclophosphamide, inhibition by cyclosporine A, and modulation by dexamethasone","volume":"144","author":"Paus","year":"1994","journal-title":"Am J Pathol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2008.228"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.12759"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2005.23787.x"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2023.02.033"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1078916"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.061164"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2023.09.004"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-023-07890-5"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2017.03.011"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201911031"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2020.05.118"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2022.12.005"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.breast.2022.04.008"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2024.06.012"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyae116"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13185397"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-023-01954-6"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1200\/JOP.17.00038"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.70021"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2018.03.056"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2018-0184"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.12788\/cutis.0215"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2022.1113"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol31090423"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.20745"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-017-4204-x"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2009.09043.x"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/brv.12767"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27490"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2018.03.007"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2018.5071"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-021-06748-y"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1188\/25.ONF.126-136"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1188\/22.CJON.190-197"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c00623"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-0715"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.TARG-19-C064"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2025.125356"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35089-5"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1007\/s40266-022-01005-1"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-1741"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-022-01324-x"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aao3003"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04356-9"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(20)31081-9"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1080\/13696998.2021.2020570"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0204-y"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35727-y"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a035931"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21561"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1002\/ijgo.13881"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1111\/ics.12521"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2020.1817441"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15038-9"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201300166"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.18479"},{"issue":"6","key":"B62","first-page":"1601","article-title":"Analysis of apoptosis during hair follicle regression (catagen)","volume":"151","author":"Lindner","year":"1997","journal-title":"Am J Pathol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2009.00939.x"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207528"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-022-01750-z"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2008.47"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-99652-8"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2021.102711"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1111\/ics.12923"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-020-02178-8"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05973-0"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1999.9325"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-022-00988-z"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16050984"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2020.12.019"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1038\/JID.2015.358"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700486"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700170"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2018.10.002"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2017.09.047"},{"key":"B81","article-title":"Toxicity spectrum of taxanes: A safety analysis from pre-marketing to post-marketing","author":"Zhao","journal-title":"Expert Opin Drug Saf"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdrv.2024.06.002"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2002.124088"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2003.06.014"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1111\/apha.14188"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.22037\/uj.v21i.8030"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2023-0513"},{"issue":"3","key":"B88","first-page":"221","article-title":"Study of different phases in growth cycle of human bone marrow cells and their growth speed, using rat-human cell hybridization, premature chromosome condensation, and sister chromatid differentiation techniques","volume":"16","author":"Zhang","year":"1988","journal-title":"Exp Hematol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(94)90037-X"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.08.1734"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1111\/ecc.13395"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1007\/s13555-025-01378-2"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2009.5"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0318811"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.34288"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-1136"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.148392"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.4161\/cc.27818"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2173"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03327-7"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2023.04.015"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1038\/JID.2015.354"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2009.148"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1172\/JCI26043"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22204"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2006.00471.x"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2009.01041.x"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2018.09.001"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-019-01889-x"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.12968\/bjon.2011.20.Sup5.S4"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0648-3_9"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12836"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2006.00510.x"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.05.118"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0227817"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1111\/ics.12589"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1159\/000528402"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2017.12.019"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.18.8764"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-017-0563-z"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202256574"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2024.103217"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1093\/bjd\/ljaf060"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2021.02.747"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2003705"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jidsp.5640233"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12700"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1111\/exd.14740"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.1.449"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.3390\/nu14163357"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0303742"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2025.1556431"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/174447\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T16:35:20Z","timestamp":1779208520000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/174447"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,1]]},"references-count":132,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,3,5]]},"published-print":{"date-parts":[[2026,5,1]]}},"alternative-id":["10.1172\/JCI174447"],"URL":"https:\/\/doi.org\/10.1172\/jci174447","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,1]]},"article-number":"e174447"}}