Fig. 4: Targeting ferroptosis to treat EC.
From: Exploring the role of ferroptosis in esophageal cancer: mechanisms and therapeutic implications
a GPX4 inhibitors inhibits GPX4 functions mainly through binding to its active site or degrading it and induce ferroptosis. b NRF2 regulates EC ferroptosis in many aspects, high levels of NRF2 are often associated with poor prognosis. polygalacin D, liensinine and ARF can inhibit the expression of NRF2. c radiotherapy induces the activation of P53, suppresses the expression of SLC7A11, leading to EC cell ferroptosis. d YAP mediates the expression of transferrin receptor 1 (TFRC) and ACSL4, in turns regulates sensitivity to ferroptosis, high levels of YAP often indicate poor OS and PFS. e DNAJB6 induce ferroptosis through down-regulating GPX4. f several compounds have been identified as inhibitors of SLC7A11 and shown significant treatment effect, including the ferroptosis-inducing agent erastin, sulfasalazine, cisplatin, sorafenib, and artesunate. g oridonin and brusatol, two kinds of diterpenoid, can induce EC cell ferroptosis by GPX4 and NRF2 pathway. h ceRNA is a hotspot in EC ferroptosis researches, providing various target for treatment. i radiotherapy, and chemotherapy showed great effect in EC ferroptosis, it is more significant when combined. In recent years, breakthrough progress has been made in the application of immunotherapy in patients with EC. Prognosis model has shown that ferroptosis positively correlates with immune activation. The combination of radiotherapy, chemotherapy and immunotherapy has great therapeutic potential in EC ferroptosis. 5-ALA 5-Aminolevulinic acid, ADAM23 A Disintegrin And Metalloproteinase Domain 23, AKT1 Threonine Kinase 1, ARF Auxin response factors, ARHGEF26 Rho Guanine Nucleotide Exchange Factor 26, BBOX-AS1 Gamma-Butyrobetaine Hydroxylase 1-Antisense RNA 1, CAMK Calcium–calmodulin dependent protein kinase, CRL Cullin-RING ligases, DNAJB6 DnaJ Heat Shock Protein Family (Hsp40) Member B6, FZD3 Frizzled Class Receptor 3, HSP Heat shock protein, MRE Meiotic Recombination, PARK Parkinson disease protein, PTGS2 prostaglandin-endoperoxide synthase 2, SAT serine acetyltransferase, TMEM161B Transmembrane Protein 161B, TNPO1 Transportin 1, YAP yes-associated protein.
