Metabolism-regulated ferroptosis in cancer progression and therapy

Cell Death and Disease, Год журнала: 2024, Номер 15(3)

Опубликована: Март 8, 2024

Abstract Cancer metabolism mainly includes carbohydrate, amino acid and lipid metabolism, each of which can be reprogrammed. These processes interact with other to adapt the complicated microenvironment. Ferroptosis is a regulated cell death induced by iron-dependent peroxidation, morphologically different from apoptosis, necrosis, necroptosis, pyroptosis, autophagy-dependent cuprotosis. plays opposite roles in ferroptosis. On one hand, carbohydrate produce NADPH maintain GPX4 FSP1 function, provide substrates for synthesizing GPX4; on might synthesize PUFAs trigger The mechanisms through cancer affects ferroptosis have been investigated extensively long time; however, some not yet elucidated. In this review, we summarize interaction between Importantly, were most concerned how these targets utilized therapy.

Язык: Английский

---

Ferroptosis in Non-Small Cell Lung Cancer: Progression and Therapeutic Potential on It

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(24), С. 13335 - 13335

Опубликована: Дек. 11, 2021

As a main subtype of lung cancer, the current situation non-small cell cancer (NSCLC) remains severe worldwide with 19% survival rate at 5 years. conventional therapy approaches, such as chemotherapy, radiotherapy, targeted therapy, and immunotherapy, gradually develop into resistance, searching for novel therapeutic strategy NSCLC is urgent. Ferroptosis, an iron-dependent programmed necrosis, has now been widely considered key factor affecting tumorigenesis progression in various cancers. Focusing on its effect NSCLC, different situations, ferroptosis can be triggered or restrained. When was induced it available to inhibit tumor both vitro vivo. The dominating mechanism due regulation classic ferroptosis-repressed GSH-dependent GPX4 signaling pathway instead other fractional regulating signal axes that regulated via impacting ROS, cellular iron levels, etc. In terms prevention GSH-independent also discovered, interestingly exhibiting same upstream signaling. addition, this review summarizes elaborates their association specific mechanisms through bioinformatics analysis multiple experimental evidence from cascades. Finally, points out possibility working resistance emphasizing potential.

Язык: Английский

---

The interplay of oncogenic signaling, oxidative stress and ferroptosis in cancer

International Journal of Cancer, Год журнала: 2023, Номер 153(5), С. 918 - 931

Опубликована: Фев. 27, 2023

Abstract Oncogene‐induced hyper‐proliferation in cancer cells is accompanied by the onset of different stresses, including DNA‐replication stress, metabolic stress and oxidative stress. Excessive accumulation reactive oxygen species (ROS) plays a pivotal contradictory role tumor progression. ROS dictates multitude cell signaling pathways to facilitate malignant transformation cells. In meantime, burden mandates reinforcing antioxidant capacity mitigate detrimental damages. The addiction increased iron demands also impinges on sensitivity ferroptosis. Targeting redox homeostasis ferroptosis overcome drug resistance treatment has become an attractive research topic. However, roles oncogenic regulation have not been comprehensively discussed. this review, we summarize current knowledge regarding interplay between context biology. We emphasize implication regulation. provide overview strategies targeting treatment.

Язык: Английский

---

Molecular subtypes of lung adenocarcinoma patients for prognosis and therapeutic response prediction with machine learning on 13 programmed cell death patterns

Journal of Cancer Research and Clinical Oncology, Год журнала: 2023, Номер 149(13), С. 11351 - 11368

Опубликована: Июнь 28, 2023

Язык: Английский

---

A Prognostic Risk Score Based on Hypoxia-, Immunity-, and Epithelialto-Mesenchymal Transition-Related Genes for the Prognosis and Immunotherapy Response of Lung Adenocarcinoma

Frontiers in Cell and Developmental Biology, Год журнала: 2022, Номер 9

Опубликована: Янв. 24, 2022

Background: Lung adenocarcinoma (LUAD), the most common subtype of non-small cell lung cancer (NSCLC), is associated with poor prognosis. However, current stage-based clinical methods are insufficient for survival prediction and decision-making. This study aimed to establish a novel model evaluating risk LUAD based on hypoxia, immunity, epithelial-mesenchymal transition (EMT) gene signatures. Methods: In this study, we used data from TCGA-LUAD training cohort GSE68465 GSE72094 validation cohorts. Immunotherapy datasets GSE135222, GSE126044, IMvigor210 were obtained previous study. Using bioinformatic machine algorithms, established immune, EMT signatures, which was then divide patients into high low groups. We analyzed differences in enriched pathways between two groups, following investigated whether score correlated stemness scores, genes related m6A, m5C, m1A m7G modification, immune microenvironment, immunotherapy response, multiple anti-cancer drug sensitivity. Results: Overall differed significantly high-risk low-risk groups (HR = 4.26). The AUCs predicting 1-, 3-, 5-year 0.763, 0.766, 0.728, respectively. dataset, HR 2.03, while 0.69, 0.651, 0.618, corresponding values dataset an 2.36 0.653, 0.662, 0.749, could independently predict OS LUAD, highly scores numerous modification-related genes. Furthermore, microenvironment characteristics. GSE135222 4.26 AUC 0.702. Evaluation GSE126044 cohorts indicated that PD-1/PD-LI inhibitor treatment may be therapy various drugs scores. Conclusion: Our developed signatures can aid prognosis guiding LUAD.

Язык: Английский

---

Prognostic Ferroptosis-Related lncRNA Signatures Associated With Immunotherapy and Chemotherapy Responses in Patients With Stomach Cancer

Frontiers in Genetics, Год журнала: 2022, Номер 12

Опубликована: Янв. 3, 2022

Ferroptosis is associated with the prognosis and therapeutic responses of patients various cancers. LncRNAs are reported to exhibit antitumor or oncogenic functions. Currently, few studies have assessed combined effects ferroptosis lncRNAs on therapy stomach cancer. In this study, transcriptomic clinical data were downloaded from TCGA database, ferroptosis-related genes obtained FerrDb database. Through correlation analysis, Cox Lasso algorithm, 10 prognostic (AC009299.2, AC012020.1, AC092723.2, AC093642.1, AC243829.4, AL121748.1, FLNB-AS1, LINC01614, LINC02485, LINC02728) screened construct a model, which was verified in two test cohorts. Risk scores for cancer calculated, divided into risk groups. The low-risk group, based median value, had longer overall survival time KM curve, lower proportion dead distribution curve. Potential mechanisms possible functions revealed using GSEA ceRNA network. By integrating information, association between features analyzed several affecting identified. Then, nomogram developed predict rates, its good predictive performance indicated by relatively high C-index (0.67118161) match calibration curves. Next, these explored. Patients group an immune-activating environment, higher immune scores, TMB, TIDE expression checkpoints, suggesting they might receive greater benefit checkpoint inhibitor therapy. addition, significant difference sensitivity mitomycin. C, cisplatin, docetaxel, but not etoposide paclitaxel, observed. summary, model guiding significance personalized It helped screen who immunotherapy guided selection chemotherapeutic drugs.

Язык: Английский

---

Machine Learning-Based Integration Develops a Macrophage-Related Index for Predicting Prognosis and Immunotherapy Response in Lung Adenocarcinoma

Archives of Medical Research, Год журнала: 2023, Номер 54(7), С. 102897 - 102897

Опубликована: Окт. 19, 2023

Язык: Английский

---

Immune, metabolic landscapes of prognostic signatures for lung adenocarcinoma based on a novel deep learning framework

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Янв. 4, 2024

Abstract Lung adenocarcinoma (LUAD) is a malignant tumor with high lethality, and the aim of this study was to identify promising biomarkers for LUAD. Using TCGA-LUAD dataset as discovery cohort, novel joint framework VAEjMLP based on variational autoencoder (VAE) multilayer perceptron (MLP) proposed. And Shapley Additive Explanations (SHAP) method introduced evaluate contribution feature genes classification decision, which helped us develop biologically meaningful biomarker potential scoring algorithm. Nineteen LUAD were identified, involved in regulation immune metabolic functions A prognostic risk model constructed by HLA-DRB1, SCGB1A1, HLA-DRB5 screened Cox regression analysis, dividing patients into high-risk low-risk groups. The validated external datasets. group characterized enrichment pathways higher infiltration compared group. While, accompanied an increase pathway activity. There significant differences between high- groups reprogramming aerobic glycolysis, amino acids, lipids, well angiogenic activity, epithelial-mesenchymal transition, tumorigenic cytokines, inflammatory response. Furthermore, more sensitive Afatinib, Gefitinib, Gemcitabine predicted pRRophetic This provides signatures capable revealing landscapes LUAD, may shed light identification other cancer biomarkers.

Язык: Английский

---

Ferroptosis in age-related vascular diseases: Molecular mechanisms and innovative therapeutic strategies

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 173, С. 116356 - 116356

Опубликована: Фев. 29, 2024

Aging, an inevitable aspect of human existence, serves as one the predominant risk factors for vascular diseases. Delving into mystery disease's pathophysiology, profound involvement programmed cell death (PCD) has been extensively demonstrated. PCD is a fundamental biological process that plays crucial role in both normal physiology and pathology, including recently discovered form, ferroptosis. Ferroptosis characterized by its reliance on iron lipid peroxidation, significant disease pathophysiology increasingly acknowledged. This phenomenon not only offers promising therapeutic target but also deepens our understanding complex relationship between ferroptosis age-related Consequently, this article aims to thoroughly review mechanisms enable effective control inhibition It focuses genetic pharmacological interventions, with goal developing innovative strategies combat

Язык: Английский

---

Ferroptosis: Molecular perspective, cellular influence, cancer manifestation, and therapeutic potentials

Journal of Drug Delivery Science and Technology, Год журнала: 2024, Номер 100, С. 105998 - 105998

Опубликована: Июль 31, 2024

Язык: Английский

---