# Progress of targeted FOX family therapy in ovarian cancer

**Authors:** Hairong Zhang, Cuiping Gong, Xin Lv

PMC · DOI: 10.3389/fphar.2025.1604998 · Frontiers in Pharmacology · 2025-07-17

## TL;DR

This paper reviews how targeting the FOX family of proteins could lead to new treatments for ovarian cancer.

## Contribution

The paper provides a comprehensive overview of the FOX family's role in ovarian cancer and recent therapeutic advances.

## Key findings

- FOX family proteins regulate key processes in ovarian cancer progression.
- Dysregulation of FOX proteins is linked to cancer proliferation and drug resistance.
- Targeting FOX proteins offers potential for new therapeutic strategies in ovarian cancer.

## Abstract

Ovarian cancer (OC) remains one of the most lethal malignancies affecting women, largely due to its asymptomatic onset and the consequent challenges in early detection and diagnosis. This often results in delayed treatment and poor clinical outcomes. Among gynecological cancers, OC exhibits the highest mortality rate. While current therapeutic approaches such as surgery and chemotherapy provide initial clinical benefit, they are frequently undermined by high rates of recurrence and metastasis. Moreover, the pronounced heterogeneity of OC further complicates treatment, highlighting the urgent need for novel therapeutic targets and more effective strategies. The forkhead box (FOX) family of transcription factors comprises a large group of proteins involved in regulating gene expression across various biological processes. Dysregulation of FOX family members has been implicated in aberrant cellular behaviors, including uncontrolled proliferation, resistance to apoptosis, enhanced invasiveness, metastatic potential, and the development of drug resistance. Importantly, the functional roles of individual FOX proteins vary significantly depending on the tumor context, reflecting the functional diversity of this family. This review aims to provide a comprehensive overview of the emerging roles of FOX family members in the pathogenesis and progression of OC, as well as recent advances in FOX-targeted therapeutic strategies.

## Linked entities

- **Diseases:** ovarian cancer (MONDO:0005140)

## Full-text entities

- **Genes:** HMGB1 (high mobility group box 1) [NCBI Gene 3146] {aka HMG-1, HMG1, HMG3, SBP-1}, PROM1 (prominin 1) [NCBI Gene 8842] {aka AC133, CD133, CORD12, MCDR2, MSTP061, PROML1}, NOTCH1 (notch receptor 1) [NCBI Gene 4851] {aka AOS5, AOVD1, TAN1, hN1}, Ctnnb1 (catenin beta 1) [NCBI Gene 12387] {aka Bfc, Catnb, Mesc}, FOXC1 (forkhead box C1) [NCBI Gene 2296] {aka ARA, ASGD3, FKHL7, FREAC-3, FREAC3, IGDA}, HK2 (hexokinase 2) [NCBI Gene 3099] {aka HKII, HXK2}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, CDCA5 (cell division cycle associated 5) [NCBI Gene 113130] {aka SORORIN}, MST1 (macrophage stimulating 1) [NCBI Gene 4485] {aka D3F15S2, DNF15S2, HGFL, MSP, NF15S2}, foxm1 (forkhead box M1) [NCBI Gene 394072] {aka foxm1l, zgc:63854}, FOXQ1 (forkhead box Q1) [NCBI Gene 94234] {aka HFH1}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, PTK7 (protein tyrosine kinase 7 (inactive)) [NCBI Gene 5754] {aka CCK-4, CCK4}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, FOXA2 (forkhead box A2) [NCBI Gene 3170] {aka HNF-3-beta, HNF3B, TCF3B}, FOXA3 (forkhead box A3) [NCBI Gene 3171] {aka FKHH3, HNF3G, TCF3G}, TOMM20 (translocase of outer mitochondrial membrane 20) [NCBI Gene 9804] {aka MAS20, MOM19, TOM20}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, MIR639 (microRNA 639) [NCBI Gene 693224] {aka MIRN639, hsa-mir-639}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, IFI27 (interferon alpha inducible protein 27) [NCBI Gene 3429] {aka FAM14D, ISG12, ISG12A, P27}, MIR877 (microRNA 877) [NCBI Gene 100126314] {aka MIRN877, hsa-mir-877, miRNA877, mir-877}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, BCL6 (BCL6 transcription repressor) [NCBI Gene 604] {aka BCL5, BCL6A, LAZ3, ZBTB27, ZNF51}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, SNHG17 (small nucleolar RNA host gene 17) [NCBI Gene 388796], CDK1 (cyclin dependent kinase 1) [NCBI Gene 983] {aka CDC2, CDC28A, P34CDC2}, PVT1 (Pvt1 oncogene) [NCBI Gene 5820] {aka LINC00079, MIR1204HG, NCRNA00079, TP53LC09, onco-lncRNA-100}, SLC2A1 (solute carrier family 2 member 1) [NCBI Gene 6513] {aka CSE, DYT17, DYT18, DYT9, EIG12, GLUT}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, MIR1252 (microRNA 1252) [NCBI Gene 100302136] {aka MIRN1252, hsa-mir-1252}, FOXM1 (forkhead box M1) [NCBI Gene 2305] {aka FKHL16, FOXM1A, FOXM1B, FOXM1C, HFH-11, HFH11}, FOXP4 (forkhead box P4) [NCBI Gene 116113] {aka hFKHLA}, FOXO3 (forkhead box O3) [NCBI Gene 2309] {aka AF6q21, FKHRL1, FKHRL1P2, FOXO2, FOXO3A}, DNER (delta/notch like EGF repeat containing) [NCBI Gene 92737] {aka UNQ26, bet}, CCN2 (cellular communication network factor 2) [NCBI Gene 1490] {aka CTGF, HCS24, IBP-8, IGFBP8, KMD, NOV2}, PLIN1 (perilipin 1) [NCBI Gene 5346] {aka FPLD4, PERI, PLIN}, KRT5 (keratin 5) [NCBI Gene 3852] {aka CK5, DDD, DDD1, EBS1, EBS2, EBS2A}, FOXP2 (forkhead box P2) [NCBI Gene 93986] {aka CAGH44, SPCH1, TNRC10}, FOXO1 (forkhead box O1) [NCBI Gene 2308] {aka FKH1, FKHR, FOXO1A}, Mul1 (mitochondrial ubiquitin ligase activator of NFKB 1) [NCBI Gene 68350] {aka 0610009K11Rik, Gide, Tnrip-1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, St13 (suppression of tumorigenicity 13) [NCBI Gene 70356] {aka 1110007I03Rik, 3110002K08Rik, HIP, HOP, HSPABP, HSPABP1}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, Lamb3 (laminin, beta 3) [NCBI Gene 16780], EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, CDC25B (cell division cycle 25B) [NCBI Gene 994] {aka MPIP2}, MIR370 (microRNA 370) [NCBI Gene 442915] {aka MIRN370, hsa-mir-370, mir-370}, FOXA1 (forkhead box A1) [NCBI Gene 3169] {aka HNF3A, TCF3A}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, AR (androgen receptor) [NCBI Gene 367] {aka AIS, AR8, DHTR, HPCX3, HUMARA, HYSP1}, E2F1 (E2F transcription factor 1) [NCBI Gene 1869] {aka E2F-1, RBAP1, RBBP3, RBP3}, CCNF (cyclin F) [NCBI Gene 899] {aka FBX1, FBXO1, FTDALS5}, CCNB1 (cyclin B1) [NCBI Gene 891] {aka CCNB}, STC1 (stanniocalcin 1) [NCBI Gene 6781] {aka STC}, CCND1 (cyclin D1) [NCBI Gene 595] {aka BCL1, D11S287E, PRAD1, U21B31}, FOXR2 (forkhead box R2) [NCBI Gene 139628] {aka FOXN6}, BSG (basigin (Ok blood group)) [NCBI Gene 682] {aka 5F7, CD147, EMMPRIN, EMPRIN, HAb18G, OK}
- **Diseases:** cytotoxic (MESH:D064420), colorectal cancer (MESH:D015179), breast cancer (MESH:D001943), serous tubal intraepithelial carcinomas (MESH:D002278), carcinogenesis (MESH:D063646), peritoneal dissemination (MESH:D010538), neuroblastoma (MESH:D009447), OC (MESH:D010051), endometrioid carcinoma (MESH:D018269), tumorigenicity (MESH:D002471), clear cell carcinoma (MESH:D002292), Cancer (MESH:D009369), prostate cancer (MESH:D011471), ovarian dysfunction (MESH:D010049), lymphoma (MESH:D008223), hormone-dependent tumors (MESH:D009376), serous (MESH:D018297), ascites (MESH:D001201), lung metastasis (MESH:D009362), non-small-cell lung cancer (MESH:D002289), secondary infertility (MESH:D007246), hepatocellular carcinoma (MESH:D006528)
- **Chemicals:** platinum (MESH:D010984), Casticin (MESH:C054133), Aulosirazoles B and C (-), flavonoid (MESH:D005419), Domatinostat (MESH:C000614036), LPA (MESH:C032881), sonidegib (MESH:C561435), All-trans retinoic acid (MESH:D014212), quercetin (MESH:D011794), NB (MESH:D009556), apigenin (MESH:D047310), KPT-330 (MESH:C585161), Licartin (MESH:C511207), cisplatin (MESH:D002945), myricetin (MESH:C040015), niraparib (MESH:C545685), 4-Vinylcyclohexene diepoxide (MESH:C012606), PTX (MESH:D017239), reactive oxygen species (MESH:D017382), Thiostrepton (MESH:D013883), lipid (MESH:D008055)
- **Species:** Homo sapiens (human, species) [taxon 9606], Macaca mulatta (rhesus macaque, species) [taxon 9544], Danio rerio (leopard danio, species) [taxon 7955], Macaca (macaque, genus) [taxon 9539], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** OVCA-429 — Homo sapiens (Human), Ovarian cystadenocarcinoma, Cancer cell line (CVCL_3936), OVCA433 — Homo sapiens (Human), Ovarian serous adenocarcinoma, Cancer cell line (CVCL_0475), OVCAR3 — Homo sapiens (Human), High grade ovarian serous adenocarcinoma, Cancer cell line (CVCL_0465), OVCA-R3 — Homo sapiens (Human), High grade ovarian serous adenocarcinoma, Cancer cell line (CVCL_1628), SKOV3 OC — Homo sapiens (Human), Ovarian serous cystadenocarcinoma, Cancer cell line (CVCL_0532), TOV112D — Homo sapiens (Human), Ovarian endometrioid adenocarcinoma, Cancer cell line (CVCL_3612), A2780 — Homo sapiens (Human), Ovarian endometrioid adenocarcinoma, Cancer cell line (CVCL_0134), TOV-21G — Homo sapiens (Human), Ovarian clear cell adenocarcinoma, Cancer cell line (CVCL_3613), CAOV3 — Homo sapiens (Human), High grade ovarian serous adenocarcinoma, Cancer cell line (CVCL_0201)

## Full text

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## Figures

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## References

99 references — full list in the complete paper: https://tomesphere.com/paper/PMC12310647/full.md

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Source: https://tomesphere.com/paper/PMC12310647