|Table of Contents|

Research progress on ferroptosis in the treatment of urinary tract tumors

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

2023 13
Research Field:
Publishing date:


Research progress on ferroptosis in the treatment of urinary tract tumors
GAO ShengMIAO BailiangMO QizhouZHAO YuwanLIU Jianjun
Department of Urology,Affiliated Hospital of Guangdong Medical University,Guangdong Zhanjiang 524001,China.
ferroptosisurologic malignanciesprostate cancerkidney cancerbladder cancer
Ferroptosis is a programmed cell death mode different from apoptosis,autophagy,and necrosis.Studies have shown that ferroptosis is associated with degenerative diseases,ischemia-reperfusion injury,kidney injury,tumors and other diseases.The incidence of urinary tract tumors is increasing year by year,and the treatment effect is not good.Therefore,exploring the potential therapeutic effect of ferroptosis in urinary tract tumors may serve as a new treatment modality.This article mainly summarizes the development history,core mechanism,and research status of ferroptosis in urinary tract tumors.Combining ferroptosis with existing tumor treatment modalities can help increase its antitumor therapy and overcome tumor resistance.However,there are relatively few studies on ferroptosis in urinary tumors,and in-depth exploration of its mechanism of action will help to apply it to clinical anti-tumor therapy.


[1] SUNG H,FERLAY J,SIEGEL RL,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA-A Cancer Journal for Clinicians,2021,71(3):209-249.
[2] TAN S,SCHUBERT D,MAHER P.Oxytosis:A novel form of programmed cell death [J].Current Topics in Medicinal Chemistry,2001,1(6):497-506.
[3] DOLMA S,LESSNICK SL,HAHN WC,et al.Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells[J].Cancer Cell,2003,3(3):285-296.
[4] YANG WS,STOCKWELL BR.Synthetic lethal screening identifies compounds activating iron-dependent,nonapoptotic cell death in oncogenic-RAS-harboring cancer cells[J].Chemistry & Biology,2008,15(3):234-245.
[5] DIXON SJ,LEMBERG KM,LAMPRECHT MR,et al.Ferroptosis:an iron-dependent form of nonapoptotic cell death[J].Cell,2012,149(5):1060-1072.
[6] YANG WS,SRIRAMARATNAM R,WELSCH ME,et al.Regulation of ferroptotic cancer cell death by GPX4[J].Cell,2014,156(1-2):317-331.
[7] JIANG X,STOCKWELL BR,CONRAD M.Ferroptosis:mechanisms,biology and role in disease[J].Nature Reviews Molecular Cell Biology,2021,22(4):266-282.
[8] ANTHONYMUTHU TS,TYURUNA YY,SUN WY,et al.Resolving the paradox of ferroptotic cell death:Ferrostatin-1 binds to 15LOX/PEBP1 complex,suppresses generation of peroxidized ETE-PE,and protects against ferroptosis[J].Redox Biology,2021,38:101744.
[9] LEE JY,KIM WK,BAE KH,et al.Lipid metabolism and ferroptosis[J].Biology,2021,10(3):184.
[10] GAO M,MONNIAN P,QUADR N,et al.Glutaminolysis and transferrin regulate ferroptosis[J].Molecular Cell,2015,59(2):298-308.
[11] WANG Y,LIU Y,LIU J,et al.NEDD4L-mediated LTF protein degradation limits ferroptosis[J].Biochemical and Biophysical Research Communications,2020,531(4):581-587.
[12] HONG X,ROH W,SULLIVAN RJ,et al.The lipogenic regulator SREBP2 induces transferrin in circulating melanoma cells and suppresses ferroptosis[J].Cancer Discovery,2021,11(3):678-695.
[13] GENG N,SHI BJ,LI SL,et al.Knockdown of ferroportin accelerates erastin-induced ferroptosis in neuroblastoma cells[J].European Review for Medical and Pharmacological Sciences,2018,22(12):3826-3836.
[14] BROWN CW,AMANTE JJ,CHHOY P,et al.Prominin2 drives ferroptosis resistance by stimulating iron export[J].Developmental Cell,2019,51(5):575-586.
[15] GAO M,MONIAN P,PAN Q,et al.Ferroptosis is an autophagic cell death process[J].Cell Research,2016,26(9):1021-1032.
[16] CHEN X,KANG R,KROEMER G,et al.Broadening horizons:the role of ferroptosis in cancer[J].Nature Reviews Clinical Oncology,2021,18(5):280-296.
[17] HONG T,LEI G,CHEN X,et al.PARP inhibition promotes ferroptosis via repressing SLC7A11 and synergizes with ferroptosis inducers in BRCA-proficient ovarian cancer[J].Redox Biology,2021,42:101928.
[18] ZHANG X,SUI S,WANG L,et al.Inhibition of tumor propellant glutathione peroxidase 4 induces ferroptosis in cancer cells and enhances anticancer effect of cisplatin[J].Journal of Cellular Physiology,2020,235(4):3425-3437.
[19] ZOU Y,PALTE MJ,DEIK AA,et al.A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis[J].Nature Communications,2019,10(1):1617.
[20] MIESS H,DANKWORTH B,GOUW AM,et al.The glutathione redox system is essential to prevent ferroptosis caused by impaired lipid metabolism in clear cell renal cell carcinoma[J].Oncogene,2018,37(40):5435-5450.
[21] TAN SK,MAHMUD I,FONTANESI F,et al.Obesity-dependent adipokine chemerin suppresses fatty acid oxidation to confer ferroptosis resistance[J].Cancer Discovery,2021,11(8):2072-2093.
[22] GREEN YS,FERREIRA DOS SANTOS MC,FUJA DG,et al.ISCA2 inhibition decreases HIF and induces ferroptosis in clear cell renal carcinoma[J].Oncogene,2022,41(42):4709-4723.
[23] MORI M,TRIBOULET R,MOHSENI M,et al.Hippo signaling regulates microprocessor and links cell-density-dependent miRNA biogenesis to cancer[J].Cell,2014,156(5):893-906.
[24] YANG WH,DING CC,SUN T,et al.The Hippo pathway effector TAZ regulates ferroptosis in renal cell carcinoma[J].Cell Reports,2019,28(10):2501-2508.
[25] XU CL,CHEN L,LI D,et al.Acyl-CoA thioesterase 8 and 11 as novel biomarkers for clear cell renal cell carcinoma[J].Front Genet,2020,11:594969.
[26] YANG WH,LIN CC,WU J,et al.The Hippo pathway effector YAP promotes ferroptosis via the E3 ligase SKP2[J].Mol Cancer Res,2021,19(6):1005-1014.
[27] ZHANG Y,LI Y,QIU Q,et al.MITD1 deficiency suppresses clear cell renal cell carcinoma growth and migration by inducing ferroptosis through the TAZ/SLC7A11 pathway[J].Oxid Med Cell Longev,2022,2022:7560569.
[28] MOU Y,WU J,ZHANG Y,et al.Low expression of ferritinophagy-related NCOA4 gene in relation to unfavorable outcome and defective immune cells infiltration in clear cell renal carcinoma[J].BMC Cancer,2021,21(1):18.
[29] WANG J,YIN X,HE W,et al.SUV39H1 deficiency suppresses clear cell renal cell carcinoma growth by inducing ferroptosis[J].Acta Pharm Sin B,2021,11(2):406-419.
[30]LI Y,ZHANG Y,QIU Q,et al.Energy-stress-mediated AMPK activation promotes GPX4-dependent ferroptosis through the JAK2/STAT3/P53 axis in renal cancer[J].Oxid Med Cell Longev,2022,2022:2353115.
[31] LEE H,ZANDKARIMI F,ZHANG Y,et al.Energy-stress-mediated AMPK activation inhibits ferroptosis[J].Nat Cell Biol,2020,22(2):225-234.
[32] MARKOWITSCH SD,SCHUPP P,LAUCKNER J,et al.Artesunate inhibits growth of sunitinib-resistant renal cell carcinoma cells through cell cycle arrest and induction of ferroptosis[J].Cancers (Basel),2020,12(11):3150.
[33] WANG YY,SHI GW,SHI SF,et al.Everolimus accelerates Erastin and RSL3-induced ferroptosis in renal cell carcinoma[J].Gene,2022,809:145992.
[34] NI W,LI Y,LIANG L,et al.Tumor microenvironment-responsive nanodrug for clear-cell renal cell carcinoma therapy via triggering waterfall-like cascade ferroptosis[J].J Biomed Nanotechnol,2022,18(2):327-342.
[35] YI J,ZHU J,WU J,et al.Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis[J].Proceedings of the National Academy of Sciences of the United States of America,2020,117(49):31189-31197.
[36] NASSAR ZD,MAH CY,DEHAIRS J,et al.Human DECR1 is an androgen-repressed survival factor that regulates PUFA oxidation to protect prostate tumor cells from ferroptosis[J].Elife,2020,9:e54166.
[37] BLOMME A,FORD CA,MUI E,et al.2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer[J].Nature Communications,2020,11(1):2508.
[38] GHOOCHANI A,HSU EC,ASLAN M,et al.Ferroptosis inducers are a novel therapeutic approach for advanced prostate cancer[J].Cancer Research,2021,81(6):1583-1594.
[39] TOUSIGNANT KD,ROCKSTROH A,POAD BLJ,et al.Therapy-induced lipid uptake and remodeling underpin ferroptosis hypersensitivity in prostate cancer[J].Cancer Metabolism,2020,8:11.
[40] YANG Y,LIU T,HU C,et al.Ferroptosis inducer erastin downregulates androgen receptor and its splice variants in castration resistant prostate cancer[J].Oncology Reports,2021,45(4):25.
[41] KIM KS,CHOI B,CHOI H,et al.Enhanced natural killer cell ant-tumor activity with nanoparticles mediated ferroptosis and potential therapeutic application in prostate cancer[J].Nanobiotechnology,2022,20(1):428.
[42] GUO P,WANG L,SHANG W,et al.Intravesical in situ immunostimulatory gel for triple therapy of bladder cancer[J].ACS Applied Materials & Interfaces,2020,12(49):54367-54377.
[43] QI A,WANG C,NI S,et al.Intravesical mucoadhesive hydrogel induces chemoresistant bladder cancer ferroptosis through delivering iron oxide nanoparticles in a three-tier strategy[J].ACS Applied Materials & Interfaces,2021,13:52374-52384.
[44] JASIM KA,GESQUIERE AJ.Ultrastable and biofunctionalizable conjugated polymer nanoparticles with encapsulated iron for ferroptosis assisted chemodynamic therapy[J].Molecular Pharmaceutics,2019,16(12):4852-4866.


National Natural Science Foundation of China(No.81272833);国家自然科学基金(编号:81272833)
Last Update: 2023-05-31