Persister cancer cells: Iron addiction and vulnerability to ferroptosis
Ferroptosis is a unique type of non-apoptotic cell death resulting from the unrestrained occurrence of peroxidized phospholipids, which are subject to iron-mediated production of lethal oxygen radicals. This cell death modality has been detected across many organisms, including in mammals, where it...
Saved in:
| Published in: | Molecular cell Vol. 82; no. 4; p. 728 |
|---|---|
| Main Authors: | , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
17.02.2022
|
| Subjects: | |
| ISSN: | 1097-4164, 1097-4164 |
| Online Access: | Get more information |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Abstract | Ferroptosis is a unique type of non-apoptotic cell death resulting from the unrestrained occurrence of peroxidized phospholipids, which are subject to iron-mediated production of lethal oxygen radicals. This cell death modality has been detected across many organisms, including in mammals, where it can be used as a defense mechanism against pathogens or even harnessed by T cells to sensitize tumor cells toward effective killing. Conversely, ferroptosis is considered one of the main cell death mechanisms promoting degenerative diseases. Emerging evidence suggests that ferroptosis represents a vulnerability in certain cancers. Here, we critically review recent advances linking ferroptosis vulnerabilities of dedifferentiating and persister cancer cells to the dependency of these cells on iron, a potential Achilles heel for small-molecule intervention. We provide a perspective on the mechanisms reliant on iron that contribute to the persister cancer cell state and how this dependency may be exploited for therapeutic benefits. |
|---|---|
| AbstractList | Ferroptosis is a unique type of non-apoptotic cell death resulting from the unrestrained occurrence of peroxidized phospholipids, which are subject to iron-mediated production of lethal oxygen radicals. This cell death modality has been detected across many organisms, including in mammals, where it can be used as a defense mechanism against pathogens or even harnessed by T cells to sensitize tumor cells toward effective killing. Conversely, ferroptosis is considered one of the main cell death mechanisms promoting degenerative diseases. Emerging evidence suggests that ferroptosis represents a vulnerability in certain cancers. Here, we critically review recent advances linking ferroptosis vulnerabilities of dedifferentiating and persister cancer cells to the dependency of these cells on iron, a potential Achilles heel for small-molecule intervention. We provide a perspective on the mechanisms reliant on iron that contribute to the persister cancer cell state and how this dependency may be exploited for therapeutic benefits. Ferroptosis is a unique type of non-apoptotic cell death resulting from the unrestrained occurrence of peroxidized phospholipids, which are subject to iron-mediated production of lethal oxygen radicals. This cell death modality has been detected across many organisms, including in mammals, where it can be used as a defense mechanism against pathogens or even harnessed by T cells to sensitize tumor cells toward effective killing. Conversely, ferroptosis is considered one of the main cell death mechanisms promoting degenerative diseases. Emerging evidence suggests that ferroptosis represents a vulnerability in certain cancers. Here, we critically review recent advances linking ferroptosis vulnerabilities of dedifferentiating and persister cancer cells to the dependency of these cells on iron, a potential Achilles heel for small-molecule intervention. We provide a perspective on the mechanisms reliant on iron that contribute to the persister cancer cell state and how this dependency may be exploited for therapeutic benefits.Ferroptosis is a unique type of non-apoptotic cell death resulting from the unrestrained occurrence of peroxidized phospholipids, which are subject to iron-mediated production of lethal oxygen radicals. This cell death modality has been detected across many organisms, including in mammals, where it can be used as a defense mechanism against pathogens or even harnessed by T cells to sensitize tumor cells toward effective killing. Conversely, ferroptosis is considered one of the main cell death mechanisms promoting degenerative diseases. Emerging evidence suggests that ferroptosis represents a vulnerability in certain cancers. Here, we critically review recent advances linking ferroptosis vulnerabilities of dedifferentiating and persister cancer cells to the dependency of these cells on iron, a potential Achilles heel for small-molecule intervention. We provide a perspective on the mechanisms reliant on iron that contribute to the persister cancer cell state and how this dependency may be exploited for therapeutic benefits. |
| Author | Conrad, Marcus Rodriguez, Raphaël Schreiber, Stuart L |
| Author_xml | – sequence: 1 givenname: Raphaël surname: Rodriguez fullname: Rodriguez, Raphaël email: raphael.rodriguez@curie.fr organization: Chemical Biology of Cancer at Institut Curie, PSL Research University, CNRS UMR 3666, INSERM U1143, Paris, France. Electronic address: raphael.rodriguez@curie.fr – sequence: 2 givenname: Stuart L surname: Schreiber fullname: Schreiber, Stuart L email: stuart_schreiber@harvard.edu organization: Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA 02142, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: stuart_schreiber@harvard.edu – sequence: 3 givenname: Marcus surname: Conrad fullname: Conrad, Marcus email: marcus.conrad@helmholtz-muenchen.de organization: Institute of Metabolism and Cell Death, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Pirogov National Research Medical University, Laboratory of Experimental Oncology, Moscow 117997, Russia. Electronic address: marcus.conrad@helmholtz-muenchen.de |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34965379$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNj01LxDAYhIOsuB_6D0R69NKapM1Hvcmi68KCHvRc0uQtZGmTNUmF_fd2cQUPw8zhYZhZopnzDhC6JbggmPCHfTH4XkNfUExJQWiBMblAC4JrkVeEV7N_eY6WMe4noGKyvkLzsqo5K0W9QJt3CNHGBCHTyumTQd_Hx2wbvMuUMVYne0rOZN9j7yCo1vY2HbPksw5C8Ifkp4JrdNmpPsLN2Vfo8-X5Y_2a79422_XTLtes5invpBAd4aRTmLHSKNwZKkWpjZEt1hJAUxBatiWItiUKKDfSTCQDQyteA12h-9_eQ_BfI8TUDDaeJisHfowN5YRVgk2a0LszOrYDmOYQ7KDCsfk7T38AzjlgtQ |
| CitedBy_id | crossref_primary_10_1016_j_redox_2025_103864 crossref_primary_10_3390_cancers16030512 crossref_primary_10_3389_fphar_2024_1418456 crossref_primary_10_1186_s12951_024_02376_w crossref_primary_10_1038_s41586_022_05022_3 crossref_primary_10_1038_s41568_024_00737_z crossref_primary_10_1016_j_tcb_2024_07_005 crossref_primary_10_3389_fphar_2025_1586578 crossref_primary_10_1126_sciadv_adx6587 crossref_primary_10_1038_d41586_025_01337_z crossref_primary_10_1038_s41586_023_06017_4 crossref_primary_10_1038_s41571_023_00815_5 crossref_primary_10_1016_j_ejmech_2023_115343 crossref_primary_10_1097_HC9_0000000000000246 crossref_primary_10_3390_cancers15215159 crossref_primary_10_1038_s41420_023_01430_0 crossref_primary_10_31083_FBL39675 crossref_primary_10_1038_s42255_025_01352_4 crossref_primary_10_3389_fonc_2024_1424218 crossref_primary_10_2147_IJN_S441112 crossref_primary_10_1038_s41467_023_41462_9 crossref_primary_10_1038_s41589_024_01612_6 crossref_primary_10_1016_j_molcel_2024_10_028 crossref_primary_10_1016_j_biopha_2024_116697 crossref_primary_10_3390_biomedicines12122728 crossref_primary_10_1016_j_ijpharm_2024_124517 crossref_primary_10_1111_jcmm_18587 crossref_primary_10_1016_j_nano_2023_102714 crossref_primary_10_1042_BST20230550 crossref_primary_10_3390_ijms241914672 crossref_primary_10_1111_imr_13301 crossref_primary_10_3892_ijmm_2024_5480 crossref_primary_10_1016_j_cbi_2024_110995 crossref_primary_10_1039_D3BM01894F crossref_primary_10_3389_fimmu_2022_1038225 crossref_primary_10_1016_j_bbcan_2022_188749 crossref_primary_10_1016_j_bioorg_2025_108396 crossref_primary_10_1016_j_critrevonc_2022_103887 crossref_primary_10_1016_j_critrevonc_2023_103964 crossref_primary_10_1016_j_ebiom_2025_105646 crossref_primary_10_1016_j_taap_2025_117460 crossref_primary_10_1002_mco2_70357 crossref_primary_10_1038_s41392_024_01891_4 crossref_primary_10_1016_j_canlet_2022_215854 crossref_primary_10_3390_ijms25168941 crossref_primary_10_1016_j_chembiol_2023_09_006 crossref_primary_10_1016_j_talanta_2023_124628 crossref_primary_10_1039_D2NR05449C crossref_primary_10_1016_j_canlet_2024_217046 crossref_primary_10_1038_d41586_024_03721_7 crossref_primary_10_1016_j_ejphar_2023_175497 crossref_primary_10_1002_path_6393 crossref_primary_10_1038_s12276_023_01077_y crossref_primary_10_1016_j_canlet_2023_216152 crossref_primary_10_3390_molecules27133970 crossref_primary_10_1038_s41388_024_02949_x crossref_primary_10_1021_acsami_4c04604 crossref_primary_10_1016_j_biochi_2025_06_013 crossref_primary_10_1016_j_ceca_2024_102966 crossref_primary_10_3389_fimmu_2025_1549600 crossref_primary_10_1038_s43018_023_00571_6 crossref_primary_10_1016_j_semcdb_2023_11_003 crossref_primary_10_1073_pnas_2401579121 crossref_primary_10_1080_10715762_2023_2244155 crossref_primary_10_1038_s41419_025_07985_3 crossref_primary_10_1016_j_intimp_2025_115188 crossref_primary_10_1002_ctm2_752 crossref_primary_10_3390_cancers15020423 crossref_primary_10_1038_s41419_025_07330_8 crossref_primary_10_1021_jacs_2c03973 crossref_primary_10_1016_j_devcel_2025_02_004 crossref_primary_10_1038_s41416_022_01998_x crossref_primary_10_1177_0271678X241252110 crossref_primary_10_26599_NR_2025_94907314 crossref_primary_10_1089_ars_2024_0608 crossref_primary_10_1038_s41388_024_03050_z crossref_primary_10_1038_s41388_025_03459_0 crossref_primary_10_1016_j_jconrel_2025_02_068 crossref_primary_10_1016_j_canlet_2024_216728 crossref_primary_10_1007_s13105_025_01078_7 crossref_primary_10_1021_jacs_3c01852 crossref_primary_10_1016_j_cyto_2023_156382 crossref_primary_10_1111_cbdd_14565 crossref_primary_10_1093_eurheartj_ehaf374 crossref_primary_10_1016_j_cbi_2022_110148 crossref_primary_10_1093_jpp_rgae148 crossref_primary_10_1158_1541_7786_MCR_22_0554 crossref_primary_10_1016_j_nantod_2022_101740 crossref_primary_10_3389_fonc_2022_858480 crossref_primary_10_1016_j_mehy_2022_110944 crossref_primary_10_3390_pharmaceutics17030277 crossref_primary_10_2174_0115680096284068240506095417 crossref_primary_10_1016_j_ijbiomac_2025_147257 crossref_primary_10_1080_1120009X_2023_2177808 crossref_primary_10_3389_fimmu_2025_1611375 crossref_primary_10_1016_j_apsb_2025_02_013 crossref_primary_10_3389_fonc_2023_1251561 crossref_primary_10_5306_wjco_v16_i4_104061 crossref_primary_10_1038_s41419_024_07007_8 crossref_primary_10_1038_s43018_023_00715_8 crossref_primary_10_1016_j_biopha_2023_115419 crossref_primary_10_1016_j_semcancer_2024_10_003 crossref_primary_10_1097_CAD_0000000000001620 crossref_primary_10_1038_s41467_025_58909_w crossref_primary_10_3390_cancers17030530 crossref_primary_10_1016_j_chembiol_2023_04_007 crossref_primary_10_1016_j_fct_2023_113644 crossref_primary_10_1186_s12964_023_01316_9 crossref_primary_10_1016_j_tcb_2023_04_005 crossref_primary_10_1172_JCI170027 crossref_primary_10_1002_adma_202415550 crossref_primary_10_3389_fimmu_2022_916664 crossref_primary_10_1016_j_molcel_2023_11_001 crossref_primary_10_1007_s11064_023_03963_3 crossref_primary_10_3389_fphar_2024_1383203 crossref_primary_10_2174_0109298673288408240212051401 crossref_primary_10_1016_j_bneo_2025_100122 crossref_primary_10_1016_j_phymed_2024_155673 crossref_primary_10_1038_s41419_024_07135_1 crossref_primary_10_1093_mtomcs_mfad019 crossref_primary_10_1038_s41585_024_00869_9 crossref_primary_10_1038_s43018_023_00702_z crossref_primary_10_1016_j_ijbiomac_2025_139734 crossref_primary_10_1186_s12935_024_03329_x crossref_primary_10_3892_ijo_2025_5793 crossref_primary_10_1002_adhm_202303533 crossref_primary_10_1002_biof_70024 crossref_primary_10_1016_j_bcp_2022_115239 crossref_primary_10_1016_j_freeradbiomed_2024_06_023 crossref_primary_10_1016_j_yexcr_2024_113990 crossref_primary_10_1186_s12951_023_02194_6 crossref_primary_10_3389_fcell_2022_818453 crossref_primary_10_1007_s10142_024_01329_8 crossref_primary_10_1038_s41586_025_08974_4 crossref_primary_10_3389_fimmu_2022_920059 crossref_primary_10_1038_s41586_024_08285_0 crossref_primary_10_3389_fimmu_2024_1442788 crossref_primary_10_1016_j_biomaterials_2023_122442 crossref_primary_10_1038_s41598_024_54837_9 crossref_primary_10_3390_cells13110951 crossref_primary_10_1016_j_phymed_2024_156115 crossref_primary_10_1002_cbic_202400211 crossref_primary_10_1186_s12943_024_02132_6 crossref_primary_10_1038_s41418_024_01350_1 crossref_primary_10_1038_s41388_022_02385_9 crossref_primary_10_1186_s12915_025_02154_6 crossref_primary_10_1038_s41420_024_01867_x crossref_primary_10_1186_s12951_025_03117_3 crossref_primary_10_1186_s12967_024_05881_6 crossref_primary_10_1007_s10495_022_01795_0 crossref_primary_10_1038_s41586_023_06255_6 crossref_primary_10_1016_j_apsb_2024_10_006 crossref_primary_10_2147_DDDT_S374328 crossref_primary_10_1016_j_pdpdt_2024_104463 |
| ContentType | Journal Article |
| Copyright | Copyright © 2021 Elsevier Inc. All rights reserved. |
| Copyright_xml | – notice: Copyright © 2021 Elsevier Inc. All rights reserved. |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1016/j.molcel.2021.12.001 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Biology |
| EISSN | 1097-4164 |
| ExternalDocumentID | 34965379 |
| Genre | Review Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NCI NIH HHS grantid: U01 CA217848 |
| GroupedDBID | --- --K -DZ -~X 0R~ 0SF 123 1~5 2WC 4.4 457 4G. 5RE 62- 7-5 AACTN AAEDT AAEDW AAFTH AAHBH AAKRW AAKUH AALRI AAMRU AAVLU AAXUO ABJNI ABMAC ABVKL ACGFO ACGFS ACNCT ADBBV ADEZE ADVLN AEFWE AENEX AEXQZ AFFNX AFTJW AGKMS AITUG AKAPO AKRWK ALMA_UNASSIGNED_HOLDINGS AMRAJ ASPBG AVWKF AZFZN BAWUL CGR CS3 CUY CVF DIK DU5 E3Z EBS ECM EIF F5P FCP FDB FEDTE FIRID HH5 HVGLF IH2 IHE IXB J1W JIG KQ8 L7B M3Z M41 N9A NPM O-L O9- OK1 P2P RCE ROL RPZ SDG SES SSZ TR2 5VS 7X8 AAYWO ABDGV ACVFH ADCNI AEUPX AFPUW AIGII AKBMS AKYEP APXCP EFKBS |
| ID | FETCH-LOGICAL-c596t-f877f161fa0553da0fd2873cdd8b0c8eec2e7c8b3e7bb1ae26d8d5535ed2469e2 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 178 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000760297000004&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1097-4164 |
| IngestDate | Sun Nov 09 10:00:27 EST 2025 Wed Feb 19 02:25:24 EST 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 4 |
| Language | English |
| License | Copyright © 2021 Elsevier Inc. All rights reserved. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c596t-f877f161fa0553da0fd2873cdd8b0c8eec2e7c8b3e7bb1ae26d8d5535ed2469e2 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23 |
| OpenAccessLink | https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=64026 |
| PMID | 34965379 |
| PQID | 2615475547 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_2615475547 pubmed_primary_34965379 |
| PublicationCentury | 2000 |
| PublicationDate | 2022-02-17 |
| PublicationDateYYYYMMDD | 2022-02-17 |
| PublicationDate_xml | – month: 02 year: 2022 text: 2022-02-17 day: 17 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Molecular cell |
| PublicationTitleAlternate | Mol Cell |
| PublicationYear | 2022 |
| SSID | ssj0014589 |
| Score | 2.687314 |
| SecondaryResourceType | review_article |
| Snippet | Ferroptosis is a unique type of non-apoptotic cell death resulting from the unrestrained occurrence of peroxidized phospholipids, which are subject to... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 728 |
| SubjectTerms | Animals Antineoplastic Agents - therapeutic use Cell Differentiation Ferroptosis - drug effects Homeostasis Humans Iron - metabolism Lipid Peroxidation - drug effects Molecular Targeted Therapy Neoplasms - drug therapy Neoplasms - metabolism Neoplasms - pathology Neoplastic Stem Cells - drug effects Neoplastic Stem Cells - metabolism Neoplastic Stem Cells - pathology Reactive Oxygen Species - metabolism Signal Transduction |
| Title | Persister cancer cells: Iron addiction and vulnerability to ferroptosis |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/34965379 https://www.proquest.com/docview/2615475547 |
| Volume | 82 |
| WOSCitedRecordID | wos000760297000004&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LS8QwEA7qKnjx_VhfRPBa7CPdpF5ExFUPLntQ2FtpkikItVnb7sL-ezNplz0Jgpf20pZ2Ms188_wIuQER8CyJtBezAIdqS-kJUNz6PBbvSh1mLBeObIKPRmIyScZdwK3uyiqXe6LbqLVRGCO_tUg_ZtwaP34__faQNQqzqx2FxjrpRRbKYEkXn6yyCCx2FHiYZPUs8GDL1jlX3_VlCgWYfAgDFxD0g99BpjM2w93_vuYe2elgJn1o9WKfrEF5QLZa4snFIXnGwndc4IoqXHZ7gqKo7-hrZUqKNUau3YFmpabzWYGTqV0R7YI2huZQVWbaGPuAI_IxfHp_fPE6SgVPxcmg8XLBeW5BXp75cRzpzM-1dZkipbWQvhIAKgSuhIyASxlkEA600PbKGHRoHWkIj8lGaUo4JTSSzJr-QZJxLphIlIgTpmWO88S0Ap70yfVSQqlVWfyMrAQzq9OVjPrkpBVzOm1na6Rufn3Ek7M_3H1OtkNsRkB6Fn5Bern9YeGSbKp581lXV04X7HE0fvsBT4q-4w |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Persister+cancer+cells%3A+Iron+addiction+and+vulnerability+to+ferroptosis&rft.jtitle=Molecular+cell&rft.au=Rodriguez%2C+Rapha%C3%ABl&rft.au=Schreiber%2C+Stuart+L&rft.au=Conrad%2C+Marcus&rft.date=2022-02-17&rft.issn=1097-4164&rft.eissn=1097-4164&rft.volume=82&rft.issue=4&rft.spage=728&rft_id=info:doi/10.1016%2Fj.molcel.2021.12.001&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1097-4164&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1097-4164&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1097-4164&client=summon |