Ferroptosis, radiotherapy, and combination therapeutic strategies

Lei, Guang; Mao, Chao; Yan, Yizhong; Li, Zhuang; Gan, Boyi

doi:10.1007/s13238-021-00841-y

Cited by 231 publications

(179 citation statements)

References 190 publications

Supporting

Mentioning

162

Contrasting

Order By: Relevance

“…Ferroptosis is a recently discovered type of regulated cell death (RCD) that differs morphologically, biochemically, and genetically from apoptosis, autophagy, and necrosis and is characterized by iron-dependent and lethal reactive oxygen species (ROS) and lipid peroxidation(LPO) accumulation [9,10]. In recent years, inducing ferroptosis in cancer cells become a latent target for cancer therapy [11][12][13], especially in those drug-tolerant and radiation resistant cancers [14,15]. Previous studies have also demonstrated that ferroptosis plays important roles in OSCC.…”

Section: Introductionmentioning

confidence: 99%

Ferroptosis-related gene signature predicts the prognosis in Oral squamous cell carcinoma patients

Zhang

Chen

et al. 2021

BMC Cancer

View full text Add to dashboard Cite

Background The prognosis of oral squamous cell carcinoma (OSCC) patients is difficult to predict or describe due to its high-level heterogeneity and complex aetiologic factors. Ferroptosis is a novel form of iron-dependent cell death that is closely related to tumour growth and progression. This study aims to clarify the predictive value of ferroptosis-related genes (FRGs) on the overall survival(OS) of OSCC patients. Methods The mRNA expression profile of FRGs and clinical information of patients with OSCC were collected from the TCGA database. Candidate differentially expressed ferroptosis-related genes (DE-FRGs) were identified by analysing differences between OSCC and adjacent normal tissues. A gene signature of prognosis-related DE-FRGs was established by univariate Cox analysis and LASSO analysis in the training set. Patients were then divided into high- and low-risk groups according to the cut-off value of risk scores, A nomogram was constructed to quantify the contributions of gene signature and clinical parameters to OS. Then several bioinformatics analyses were used to verify the reliability and accuracy of the model in the validation set. Finally, single-sample gene set enrichment analysis (ssGSEA) was also performed to reveal the underlying differences in immune status between different risk groups. Results A prognostic model was constructed based on 10 ferroptosis-related genes. Patients in high-risk group had a significantly worse OS (p < 0.001). The gene signature was verified as an independent predictor for the OS of OSCC patients (HR > 1, p < 0.001). The receiver operating characteristic curve displayed the favour predictive performance of the risk model. The prediction nomogram successfully quantified each indicator’s contribution to survival and the concordance index and calibration plots showed its superior predictive capacity. Finally, ssGSEA preliminarily indicated that the poor prognosis in the high-risk group might result from the dysregulation of immune status. Conclusion This study established a 10-ferroptosis-releated gene signature and nomogram that can be used to predict the prognosis of OSCC patients, which provides new insight for future anticancer therapies based on potential FRG targets.

show abstract

Section: Introductionmentioning

confidence: 99%

Ferroptosis-related gene signature predicts the prognosis in Oral squamous cell carcinoma patients

Zhang

Chen

et al. 2021

BMC Cancer

View full text Add to dashboard Cite

show abstract

“…[24][25][26][27] Growing evidence also reveals that ferroptosis (at least partially) contributes to the anti-cancer therapeutic effects of common cancer therapies, including radiotherapy, targeted therapies, and immunotherapy. [28][29][30][31][32][33] Importantly, cancer cells in specific cell states (such as drug-tolerant persister cancer cells or those in therapyresistant state) [34,35] or harboring certain mutations (such as mutations in E cadherin-NF2-Hippo pathway [36] ) are vulnerable to ferroptosis. Therefore, targeting ferroptosis has emerged as a promising therapeutic strategy for treating certain cancers.…”

Section: Instead Incorporation Of Mufas Into Pls Can Displace Pufas Frommentioning

confidence: 99%

mTORC1 and ferroptosis: Regulatory mechanisms and therapeutic potential

Lei

Gan

2021

BioEssays

Self Cite

View full text Add to dashboard Cite

Ferroptosis, a form of regulated cell death triggered by lipid hydroperoxide accumulation, has an important role in a variety of diseases and pathological conditions, such as cancer. Targeting ferroptosis is emerging as a promising means of therapeutic intervention in cancer treatment. Polyunsaturated fatty acids, reactive oxygen species, and labile iron constitute the major underlying triggers for ferroptosis. Other regulators of ferroptosis have also been discovered recently, among them the mechanistic target of rapamycin complex 1 (mTORC1), a central controller of cell growth and metabolism.Inhibitors of mTORC1 have been used in treating diverse diseases, including cancer. In this review, we discuss recent findings linking mTORC1 to ferroptosis, dissect mechanisms underlying the establishment of mTORC1 as a key ferroptosis modulator, and highlight the potential of co-targeting mTORC1 and ferroptosis in cancer treatment. This review will provide valuable insights for future investigations of ferroptosis and mTORC1 in fundamental biology and cancer therapy.

show abstract

“…Recently, the stimulation of ferroptosis has mushroomed as an alternative therapeutic approach to tumor suppression, especially for therapy-resistant patients (Hassannia et al, 2019;Liang et al, 2019). Ferroptosis exerts effectiveness in radiotherapy-induced cancer suppression and mediates the synergy of radiation therapy and immunotherapy (Lei et al, 2021). Apart from drivers and inducers of ferroptosis, many genes have been defined as suppressors, inhibitors, markers, and ferroptosis-disease associations (Zhou and Bao, 2020).…”

Section: Introductionmentioning

confidence: 99%

A Ferroptosis-Related Gene Model Predicts Prognosis and Immune Microenvironment for Cutaneous Melanoma

Chen

2021

Front. Genet.

View full text Add to dashboard Cite

BackgroundCutaneous melanoma is a common but aggressive tumor. Ferroptosis is a recently discovered cell death with important roles in tumor biology. Nevertheless, the prognostic power of ferroptosis-linked genes remained unclear in cutaneous melanoma.MethodsCutaneous melanoma patients of TCGA (The Cancer Genome Atlas) were taken as the training cohort while GSE65904 and GSE22153 as the validation cohorts. Multifactor Cox regression model was used to build a prognostic model, and the performance of the model was assessed. Functional enrichment and immune infiltration analysis were used to clarify the mechanisms.ResultsA five ferroptosis-linked gene predictive model was developed. ALOX5 and GCH1 were illustrated as independent predictive factors. Functional assessment showed enriched immune-linked cascades. Immune infiltrating analysis exhibited the distinct immune microenvironment.ConclusionHerein, a novel ferroptosis-related gene prognostic model was built in cutaneous melanoma. This model could be used for prognostic prediction, and maybe helpful for the targeted and immunotherapies.

show abstract

Ferroptosis, radiotherapy, and combination therapeutic strategies

Cited by 231 publications

References 190 publications

Ferroptosis-related gene signature predicts the prognosis in Oral squamous cell carcinoma patients

Ferroptosis-related gene signature predicts the prognosis in Oral squamous cell carcinoma patients

mTORC1 and ferroptosis: Regulatory mechanisms and therapeutic potential

A Ferroptosis-Related Gene Model Predicts Prognosis and Immune Microenvironment for Cutaneous Melanoma

Contact Info

Product

Resources

About