PPARα phosphorylation regulates colorectal tumor immune escape.

A high level of PD-L1 in cancer cells promotes tumor immune escape and inhibits tumor immunotherapy. Although PD-L1 gene expression is upregulated by multiple pathways, its gene transcriptional repression is still unclear. Here we found that loss of PPARα, one of the peroxisome-proliferator-activated receptors (PPARs) family members, promoted colorectal tumor immune escape. Mechanistically, PPARα directly bound to the PD-L1 promoter resulting in its gene transcriptional repression, which in turn increased T cell activity, and PPARα agonist enhanced this event. However, ERK induced PPARα-S12 phosphorylation leading to blockade of PPARα-mediated PD-L1 transcriptional repression, and the combination of ERK inhibitor with PPARα agonist significantly inhibited tumor immune escape. These findings suggest that the ERK-PPARα pathway inhibited PD-L1 gene transcriptional repression and promoted colorectal tumor immune escape.

To Investigate the Diagnostic Accuracy and Prognostic Value of Amplitude-Integrated Electroencephalography (aEEG) in Neonatal Hypoxic Ischemic Encephalopathy.

Objective: The objective of this study is to investigate the diagnostic accuracy and prognostic value of amplitude-integrated electroencephalography (aEEG) in neonatal hypoxic ischemic encephalopathy (HIE). Methods: Fifty-three neonates with HIE admitted to our hospital from February 2020 to September 2021 were included in the encephalopathy group, while 22 healthy neonates born in our hospital during the same period were included in the healthy group. The neonates were separated into three subgroups based on their aEEG results: normal, slightly abnormal, and severely abnormal. We investigated the correlation between aEEG monitoring and HIE clinical grading, as well as the rate of HIE abnormal prognosis, and we analyzed the prognostic value of aEEG in HIE. Results: The aEEGs of all neonates in the healthy group were normal. In the encephalopathy group, there were 24 neonates with normal aEEGs (including 20 with mild HIE and 4 with moderate HIE), 16 neonates with mildly abnormal aEEGs (including 4 with mild HIE, 10 with moderate HIE, and 2 with severe HIE), and 13 neonates with severely abnormal aEEGs (including 4 with moderate HIE and 9 with severe HIE). A very close correlation between aEEG monitoring results and HIE grading and prognosis was found (P < .05). The head circumference of neonates with severely abnormal aEEGs was smaller than that of the other two groups and was significantly smaller than that of the healthy group (P < .05). However, there was no significant difference in the body length and weight of neonates in the severely abnormal aEEG group when compared to other groups (P > .05). Conclusion: The brain function of neonates with HIE can be accurately diagnosed with aEEG, and this diagnostic technique has a crucial application value in the early diagnosis and prognosis evaluation of neonatal HIE.

PPARγ agonist inhibits c-Myc-mediated colorectal cancer tumor immune escape.

As a master transcription factor, c-Myc plays an important role in promoting tumor immune escape. In addition, PPARγ (peroxisome proliferator-activated receptor γ) regulates cell metabolism, inflammation, and tumor progression, while the effect of PPARγ on c-Myc-mediated tumor immune escape is still unclear. Here we found that cells treated with PPARγ agonist pioglitazone (PIOG) reduced c-Myc protein expression in a PPARγ-dependent manner. qPCR analysis showed that PIOG had no significant effect on c-Myc gene levels. Further analysis showed that PIOG decreased c-Myc protein half-life. Moreover, PIOG increased the binding of c-Myc to PPARγ, and induced c-Myc ubiquitination and degradation. Importantly, c-Myc increased PD-L1 and CD47 immune checkpoint protein expression and promoted tumor immune escape, while PIOG inhibited this event. These findings suggest that PPARγ agonist inhibited c-Myc-mediated tumor immune escape by inducing its ubiquitination and degradation.

PPARγ inhibited tumor immune escape by inducing PD-L1 autophagic degradation.

Blockade of the programmed death 1 (PD-1)/ programmed death ligand 1 (PD-L1) immune checkpoint could increase antitumor immunotherapy for multiple types of cancer, but the response rate of patients is about 10%-40%. Peroxisome proliferator activated receptor γ (PPARγ) plays an important role in regulating cell metabolism, inflammation, immunity, and cancer progression, while the mechanism of PPARγ on cancer cell immune escape is still unclear. Here we found that PPARγ expression exhibits a positive correlation with activation of T cells in non-small-cell lung cancer (NSCLC) by clinical analysis. Deficiency of PPARγ promoted immune escape of NSCLC by inhibiting T-cell activity, which was associated with increased PD-L1 protein level. Further analysis showed that PPARγ reduced PD-L1 expression independent of its transcriptional activity. PPARγ contains the microtubule-associated protein 1A/1B-light chain 3 (LC3) interacting region motif, which acts as an autophagy receptor for PPARγ binding to LC3, leading to degradation of PD-L1 in lysosomes, which in turn suppresses NSCLC tumor growth by increasing T-cell activity. These findings suggest that PPARγ inhibits the tumor immune escape of NSCLC by inducing PD-L1 autophagic degradation.

AMPK phosphorylates PPARδ to mediate its stabilization, inhibit glucose and glutamine uptake and colon tumor growth.

Peroxisome proliferator-activated receptor δ (PPARδ) is a nuclear receptor transcription factor that plays an important role in the regulation of metabolism, inflammation, and cancer. In addition, the nutrient-sensing kinase 5'AMP-activated protein kinase (AMPK) is a critical regulator of cellular energy in coordination with PPARδ. However, the molecular mechanism of the AMPK/PPARδ pathway on cancer progression is still unclear. Here, we found that activated AMPK induced PPARδ-S50 phosphorylation in cancer cells, whereas the PPARδ/S50A (nonphosphorylation mimic) mutant reversed this event. Further analysis showed that the PPARδ/S50E (phosphorylation mimic) but not the PPARδ/S50A mutant increased PPARδ protein stability, which led to reduced p62/SQSTM1-mediated degradation of misfolded PPARδ. Furthermore, PPARδ-S50 phosphorylation decreased PPARδ transcription activity and alleviated PPARδ-mediated uptake of glucose and glutamine in cancer cells. Soft agar and xenograft tumor model analysis showed that the PPARδ/S50E mutant but not the PPARδ/S50A mutant inhibited colon cancer cell proliferation and tumor growth, which was associated with inhibition of Glut1 and SLC1A5 transporter protein expression. These findings reveal a new mechanism of AMPK-induced PPARδ-S50 phosphorylation, accumulation of misfolded PPARδ protein, and inhibition of PPARδ transcription activity contributing to the suppression of colon tumor formation.

Glycolysis addiction compensating for a defective pentose phosphate pathway confers gemcitabine sensitivity in SETD2-deficient pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy driven by genetic mutations and/or epigenetic dysregulation. Gemcitabine chemotherapy is the first-line regimen for pancreatic cancer but has limited efficacy. Our previous study revealed the role of SETD2-H3K36me3 loss in the initiation and metastasis of PDAC, but little is known about its role in tumor metabolism. Here, we found that SETD2-deficient PDAC enhanced glycolysis addiction via upregulation of glucose transporter 1 (GLUT1) to meet its large demand for glucose in progression. Moreover, SETD2 deficiency impaired nucleoside synthesis by directly downregulating the transcriptional level of transketolase (TKT) in the pentose phosphate pathway. The metabolic changes confer SETD2-deficient PDAC cells with increased sensitivity to gemcitabine under glycolysis restriction conditions. Collectively, our study provides mechanistic insights into how SETD2 deficiency reprograms glycolytic metabolism to compensate for insufficient nucleoside synthesis, suggesting that glycolysis restriction combined with gemcitabine might be a potential therapeutic strategy for PDAC patients with SETD2 deficiency.

Aspirin Use and the Risk of Hepatocellular Carcinoma: A Meta-analysis.

INTRODUCTION AND AIM: The use of aspirin is a potential protective factor against the development of hepatocellular carcinoma (HCC). Therefore, we conducted a meta-analysis to evaluate the contribution of aspirin to the risk of HCC. METHODS: We searched for PubMed and EMBASE through September 2021. RESULTS: Eighteen studies (16 cohort, 2 case-control) were included. Aspirin users were less likely to develop HCC than nonusers [adjusted odds ratio (OR), 0.54; 95% confidence interval (CI): 0.44-0.66]. Stratified analysis showed that aspirin reduced the risk of HCC in Asian and Western populations (OR, 0.59 vs. 0.67). Besides, aspirin has protective effects against HCC after hepatitis B virus (OR, 0.70; 95% CI: 0.52-0.93) and hepatitis C virus infections (OR, 0.41; 95% CI: 0.23-0.73). Aspirin has protective effects on people with chronic liver disease (OR, 0.46; 95% CI: 0.31-0.67) and on the general population (OR, 0.65; 95% CI: 0.54-0.79). In addition, confounding factors have an important impact on the results of aspirin prevention of liver cancer before (OR, 0.28; 95% CI: 0.06-1.27) and after (OR, 0.58; 95% CI: 0.47-0.71) adjustment. Further studies have shown that those in the long duration group do not experience better effects in preventing HCC (OR, 0.62 vs. 0.63). A further meta-analysis of 3 articles showed that the use of aspirin did not increase the risk of bleeding in patients with HCC (OR, 1.19; 95% CI: 0.87-1.64). CONCLUSION: Our meta-analysis shows that the use of aspirin is associated with a lower risk of liver cancer.

EGFR/PPARδ/HSP90 pathway mediates cancer cell metabolism and chemoresistance.

Epidermal growth factor receptor (EGFR) induces peroxisome-proliferator-activated receptor-δ (PPARδ)-Y108 phosphorylation, while it is unclear the effect of phosphorylation of PPARδ on cancer cell metabolism. Here we found that EGF treatment increased its protein stability by inhibiting its lysosomal dependent degradation, which was reduced by gefitinib (EGFR inhibitor) treatment. PPARδ-Y108 phosphorylation in response to EGF recruited HSP90 (heat shock protein 90) to PPARδ resulting in increased PPARδ stability. In addition, PPARδ-Y108 phosphorylation promoted cancer cell metabolism, proliferation, and chemoresistance. Therefore, this study revealed a novel molecular mechanism of EGFR/HSP90/PPARδ pathway-mediated cancer cell metabolism, proliferation, and chemoresistance, which provides a strategy for cancer treatment.

Role of autophagy on cancer immune escape.

Autophagy is catabolic process by degradation of intracellular components in lysosome including proteins, lipids, and mitochondria in response to nutrient deficiency or stress such as hypoxia or chemotherapy. Increasing evidence suggests that autophagy could induce immune checkpoint proteins (PD-L1, MHC-I/II) degradation of cancer cells, which play an important role in regulating cancer cell immune escape. In addition to autophagic degradation of immune checkpoint proteins, autophagy induction in immune cells (macrophages, dendritic cells) manipulates antigen presentation and T cell activity. These reports suggest that autophagy could negatively or positively regulate cancer cell immune escape by immune checkpoint protein and antigens degradation, cytokines release, antigens generation. These controversial phenomenon of autophagy on cancer cell immune evasion may be derived from different experimental context or models. In addition, autophagy maybe exhibit a role in regulating host excessive immune response. So rational combination with autophagy could enhance the efficacy of cancer immunotherapy. In this review, the current progress of autophagy on cancer immune escape is discussed. Video Abstract.

Expanded CD14hiCD16- Immunosuppressive Monocytes Predict Disease Severity in Patients with Acute Pancreatitis.

Mild acute pancreatitis (AP) is a self-limiting disease, whereas severe AP has high mortality because of enhanced systemic inflammation and multiple organ failure. In experimental models of AP, infiltration of monocytes and activation of monocyte-derived macrophages largely determine the severity of the disease. Our previous studies have shown that CD11b+Ly-6Chi inflammatory monocytes were mobilized from bone marrow into peripheral blood and inflamed pancreas during the early stage of AP. However, the phenotype and characteristics of circulating monocytes in patients with AP are not well defined. Fifty patients with AP and nine age- and sex-matched healthy volunteers were enrolled in this study. Compared with those of healthy volunteers, the proportion of CD14hiCD16- monocytes and the level of myeloid-related cytokines/chemokines were increased in AP patients within 48 h after disease onset, especially in patients with a severe disease course. Moreover, the increased monocyte proportions were associated with decreased HLA-DR expression and a reduced T cell count. Notably, dynamic changes in circulating CD14hiCD16- monocytes and their HLA-DR expression, as well as in CD4+ T cells, were obviously different between moderate severe AP and severe AP. Last, area under the receiver operating characteristic analysis showed that the combination of CD14hiCD16- monocyte proportions with their HLA-DR level had higher accuracy for predicting the severity of AP. Taken together, the ratio of CD14hiCD16- monocytes and their HLA-DR level might assist in predicting the severity of disease in AP patients at admission and in monitoring patients' clinical status during recovery.

Loss of Setd2 promotes Kras-induced acinar-to-ductal metaplasia and epithelia-mesenchymal transition during pancreatic carcinogenesis.

OBJECTIVE: SETD2, the sole histone H3K36 trimethyltransferase, is frequently mutated or deleted in human cancer, including pancreatic ductal adenocarcinoma (PDAC). However, whether SETD2/H3K36me3 alteration results in PDAC remains largely unknown. DESIGN: TCGA(PAAD) public database and PDAC tissue array with SETD2/H3K36me3 staining were used to investigate the clinical relevance of SETD2 in PDAC. Furthermore, to define the role of SETD2 in the carcinogenesis of PDAC, we crossed conditional Setd2 knockout mice (PdxcreSetd2flox/flox) together with KrasG12D mice. Moreover, to examine the role of SETD2 after ductal metaplasia, Crisp/cas9 was used to deplete Setd2 in PDAC cells. RNA-seq and H3K36me3 ChIP-seq were performed to uncover the mechanism. RESULTS: SETD2 mutant/low expression was correlated with poor prognosis in patients with PDAC. Next, we found that Setd2 acted as a putative tumour suppressor in Kras-driven pancreatic carcinogenesis. Mechanistically, Setd2 loss in acinar cells facilitated Kras-induced acinar-to-ductal reprogramming, mainly through epigenetic dysregulation of Fbxw7. Moreover, Setd2 ablation in pancreatic cancer cells enhanced epithelia-mesenchymal transition (EMT) through impaired epigenetic regulation of Ctnna1. In addition, Setd2 deficiency led to sustained Akt activation via inherent extracellular matrix (ECM) production, which would favour their metastasis. CONCLUSION: Together, our findings highlight the function of SETD2 during pancreatic carcinogenesis, which would advance our understanding of epigenetic dysregulation in PDAC. Moreover, it may also pave the way for development of targeted, patients-tailored therapies for PDAC patients with SETD2 deficiency.

ROR2 induces cell apoptosis via activating IRE1α/JNK/CHOP pathway in high-grade serous ovarian carcinoma in vitro and in vivo.

BACKGROUND: Epithelial ovarian cancer (EOC) is the most lethal cancer in female genital tumors. New disease markers and novel therapeutic strategies are urgent to identify considering the current status of treatment. Receptor tyrosine kinases family plays critical roles in embryo development and disease progression. However, ambivalent research conclusions of ROR2 make its role in tumor confused and the underlying mechanism is far from being understood. In this study, we sought to clarify the effects of ROR2 on high-grade serous ovarian carcinoma (HGSOC) cells and reveal the mechanism. METHODS: Immunohistochemistry assay and western-blot assay were used to detect proteins expression. ROR2 overexpression adenovirus and Lentivirus were used to create ROR2 overexpression model in vitro and in vivo, respectively. MTT assay, colony formation assay and transwell assay were used to measure the proliferation, invasion and migration ability of cancer cells. Flow cytometry assay was used to detect cell apoptosis rate. Whole transcriptome analysis was used to explore the differentially expressed genes between ROR2 overexpression group and negative control group. SiRNA targeted IRE1α was used to knockdown IRE1α. Kira6 was used to inhibit phosphorylation of IRE1α. RESULTS: Expression of ROR2 was significantly lower in HGSOC tissues compared to normal fallopian tube epithelium or ovarian surface epithelium tissues. In HGSOC cohort, patients with advanced stages or positive lymph nodes were prone to express lower ROR2. Overexpression of ROR2 could repress the proliferation of HGSOC cells and induce cell apoptosis. RNA sequencing analysis indicated that ROR2 overexpression could induce unfold protein response. The results were also confirmed by upregulation of BIP and phosphorylated IRE1α. Furthermore, pro-death factors like CHOP, phosphorylated JNK and phosphorylated c-Jun were also upregulated. IRE1α knockdown or Kira6 treatment could reverse the apoptosis induced by ROR2 overexpression. Finally, tumor xenograft experiment showed ROR2 overexpression could significantly repress the growth rate and volume of transplanted tumors. CONCLUSIONS: Taken together, ROR2 downregulation was associated with HGSOC development and progression. ROR2 overexpression could repress cell proliferation and induce cell apoptosis in HGSOC cells. And the underlying mechanism might be the activation of IRE1α/JNK/CHOP pathway induced by ROR2.

PPARδ promotes tumor progression via activation of Glut1 and SLC1-A5 transcription.

Malignant cancer cell uncontrolled growth depends on the persistent nutrient availability such as glucose and amino acids, which is required for cancer cell energetic and biosynthetic pathways. As a nuclear hormone receptor, peroxisome-proliferator-activated receptor δ (PPARδ) plays a critical role in inflammation and cancer, however, it is still unclear the regulatory mechanism of PPARδ on cancer cell metabolism. Here, we found that PPARδ directly regulated neutral amino acid transporter SLC1-A5 (solute carrier family 1 member 5) and glucose transporter-1 (Glut1) gene transcription, leading to uptake of glucose and amino acid, activation of mTOR signaling, and tumor progression. In contrast, silence of PPARδ or its antagonist inhibited this event. More importantly, PPARδ promoted cancer cell metabolic reprogramming resulting in chemoresistance, which was alleviated by PPARδ antagonist. These findings revealed a novel mechanism of PPARδ-mediated tumor progression, which provided a potential strategy for cancer treatment.

PPARα Promotes Cancer Cell Glut1 Transcription Repression.

Abundant nutrient availability including glucose and amino acids plays an important role in maintaining cancer cell energetic and biosynthetic pathways. As a nuclear receptor, peroxisome-proliferator-activated receptor α (PPARα) regulates inflammation and cancer progression, however, it is still unclear the interaction of PPARα with the cancer cell glucose metabolism. Here we found that PPARα reduced Glut1 (Glucose transporter 1) protein and gene levels in HCT-116, SW480, HeLa, and MCF-7 cancer cell lines. In contrast, silenced PPARα reversed this event. Further analysis shows that PPARα directly targeted the consensus PPRE motif of Glut1 promoter region resulting in Glut1 transcription repression. PPARα-mediated Glut1 transcription repression led to decreased influx of glucose in cancer cells. These findings revealed a novel mechanism of PPARα-mediated cancer cell Glut1 transcription repression. J. Cell. Biochem. 118: 1556-1562, 2017. © 2016 Wiley Periodicals, Inc.

Caffeic acid phenethyl ester attenuates liver fibrosis via inhibition of TGF-ß1/Smad3 pathway and induction of autophagy pathway.

Caffeic acid phenethyl ester (CAPE) has been reported to possess the hepatoprotective effect. This study was to investigate the mechanism underlying CAPE against liver fibrosis in a liver fibrosis model induced by toxic carbon tetrachloride (CCl4) in male Sprague-Dawley rats and in vitro in CAPE (5 µM, 10 µM, 15 µM) treated hepatic stellate cells (HSC-T6). We found that CAPE treatment remarkably attenuated CCl4-induced liver fibrosis by blocking the activation of HSCs as determined by the expression alternation of transforming growth factor (TGF)-ß1, phosphorylated Smad3 (p-Smad3), collage I, α-smooth muscle actin (α-SMA), matrix metalloproteinases (MMPs) 2, tissue inhibitor of matrix metalloproteinases (TIMPs) 1. The hepatoprotective effects of CAPE were also associated with upregulation of autophasomes in HSCs as determined by transmission electron microscopy (TEM) detection. The in vitro study further confrimed that CAPE attenuated liver fibrogenesis via inducing authophagic markers including LC3, ATG5, Beclin 1 expressions, while inhibiting AKT/mTOR signaling in HSC-T6 cells. Thus, the protective effects of CAPE against liver fibrosis might due to the inhibition of TGF-ß1/Smad3 signaling and induction of authophagy in HSCs.

EGFR/MDM2 signaling promotes NF-κB activation via PPARγ degradation.

Dysregulated expression of epidermal growth factor receptor (EGFR) has been implicated in many cancer events, while peroxisome proliferator-activated receptor γ (PPARγ) negatively regulates cancer progression. The molecular mechanism of EGFR interaction with PPARγ is still unclear. Here, we found that nuclear EGFR induced phosphorylation of PPARγ at Tyr-74 leading to PPARγ ubiquitination and degradation by mouse double minute 2 (MDM2) ubiquitin ligase. PPARγ degradation by EGFR/MDM2 signaling resulted in accumulation of nuclear factor-kappaB (NF-κB)/p65 protein levels and increasing NF-κB activation. In contrast, PPARγ-Y74A mutant reversed this event. Moreover, PPARγ-Y74A mutant suppressed cell proliferation and increased chemotherapeutic agent-induced cancer cell sensitivity. Importantly, the clinical findings show that the nuclear phosphorylation of PPARγ-Y74 and EGFR expression in colonic cancer tissues was higher than that in control normal tissues. Thus, our study revealed a novel molecular mechanism that nuclear EGFR/NF-κB signaling promoted cell proliferation by destructing PPARγ function, which provides a novel strategy for cancer treatment.

Inhibitor of growth-4 is a potential target for cancer therapy.

The inhibitor of growth-4 (ING-4) belongs to the inhibitor of growth (ING) family that is a type II tumor suppressor gene including five members (ING1-5). As a tumor suppressor, ING4 inhibits tumor growth, invasion, and metastasis by multiple signaling pathways. In addition to that, ING4 can facilitate cancer cell sensitivity to chemotherapy and radiotherapy. Although ING4 loss is observed for many types of cancers, increasing evidences show that ING4 can be used for gene therapy. In this review, the recent progress of ING4 regulating tumorigenesis is discussed.

Algal sludge from Taihu Lake can be utilized to create novel PGPR-containing bio-organic fertilizers.

Large amounts of refloated algal sludge from Taihu Lake result in secondary environmental pollution due to annual refloatation. This study investigated the possibility to produce bio-organic fertilizer (BIO) using algal sludge as a solid-state fermentation (SSF) medium. Results showed that addition of algal sludge contributed to efficient SFF by a plant growth-promoting rhizobacteria (PGPR) strain SQR9 and improved the nutrient contents in the novel BIO. The optimum water content and initial inoculation size were 45% and 5%, respectively. After 6 days of SSF, the biomass of strain SQR9 was increased to a cell density of more than 5 × 10(7) CFU g(-1). Microcystins were rapidly degraded, and a high germination index value was observed. Plant growth experiments showed that the produced BIO efficiently promoted plant growth. Additional testing showed that the novel SSF process was also suitable for other PGPR strains. This study provides a novel way of high-value utilization of algal sludge from Taihu Lake by producing low-cost but high-quality BIOs.

Dual function of activated PPARγ by ligands on tumor growth and immunotherapy.

As one of the peroxisome-proliferator-activated receptors (PPARs) members, PPARγ is a ligand binding and activated nuclear hormone receptor, which is an important regulator in metabolism, proliferation, tumor progression, and immune response. Increased evidence suggests that activation of PPARγ in response to ligands inhibits multiple types of cancer proliferation, metastasis, and tumor growth and induces cell apoptosis including breast cancer, colon cancer, lung cancer, and bladder cancer. Conversely, some reports suggest that activation of PPARγ is associated with tumor growth. In addition to regulating tumor progression, PPARγ could promote or inhibit tumor immunotherapy by affecting macrophage differentiation or T cell activity. These controversial findings may be derived from cancer cell types, conditions, and ligands, since some ligands are independent of PPARγ activity. Therefore, this review discussed the dual role of PPARγ on tumor progression and immunotherapy.

Ferroptosis is an effective strategy for cancer therapy.

Ferroptosis is a form of intracellular iron-dependent cell death that differs from necrosis, autophagy and apoptosis. Intracellular iron mediates Fenton reaction resulting in lipid peroxidation production, which in turn promotes cell death. Although cancer cell exhibit's ability to escape ferroptosis by multiple pathways such as SLC7A11, GPX4, induction of ferroptosis could inhibit cancer cell proliferation, migration and invasion. In tumor microenvironment, ferroptosis could affect immune cell (T cells, macrophages etc.) activity, which in turn regulates tumor immune escape. In addition, ferroptosis in cancer cells could activate immune cell activity by antigen processing and presentation. Therefore, ferroptosis could be an effective strategy for cancer therapy such as chemotherapy, radiotherapy, and immunotherapy. In this paper, we reviewed the role of ferroptosis on tumor progression and therapy, which may provide a strategy for cancer treatment.