Metabolic cell death in cancer: ferroptosis, cuproptosis, disulfidptosis, and beyond

Protein & Cell, Journal Year: 2024, Volume and Issue: 15(9), P. 642 - 660

Published: Feb. 29, 2024

Abstract Cell death resistance represents a hallmark of cancer. Recent studies have identified metabolic cell as unique forms regulated resulting from an imbalance in the cellular metabolism. This review discusses mechanisms death—ferroptosis, cuproptosis, disulfidptosis, lysozincrosis, and alkaliptosis—and explores their potential cancer therapy. Our underscores complexity pathways offers insights into innovative therapeutic avenues for treatment.

Language: Английский

---

Multi‐omics analysis of disulfidptosis regulators and therapeutic potential reveals glycogen synthase 1 as a disulfidptosis triggering target for triple‐negative breast cancer

MedComm, Journal Year: 2024, Volume and Issue: 5(3)

Published: Feb. 28, 2024

Disruption of disulfide homeostasis during biological processes can have fatal consequences. Excess disulfides induce cell death in a novel manner, termed as "disulfidptosis." However, the specific mechanism disulfidptosis has not yet been elucidated. To determine cancer types sensitive to and outline corresponding treatment strategies, we firstly investigated crucial functions regulators pan-cancer at multi-omics levels. We found that different tumor expressed dysregulated levels regulators, most which had an impact on prognosis. Moreover, calculated activity score tumors validated it using multiple independent datasets. Additionally, was correlated with classic pathways various cancers. Disulfidptosis also associated immune characteristics could predict immunotherapy outcomes. Notably, regulator, glycogen synthase 1 (

Language: Английский

---

Epigenetic regulation of diverse cell death modalities in cancer: a focus on pyroptosis, ferroptosis, cuproptosis, and disulfidptosis

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: April 23, 2024

Abstract Tumor is a local tissue hyperplasia resulted from cancerous transformation of normal cells under the action various physical, chemical and biological factors. The exploration tumorigenesis mechanism crucial for early prevention treatment tumors. Epigenetic modification common important in cells, including DNA methylation, histone modification, non-coding RNA m6A modification. mode cell death programmed by death-related genes; however, recent researches have revealed some new modes death, pyroptosis, ferroptosis, cuproptosis disulfidptosis. regulation deaths mainly involved key proteins affects up-regulating or down-regulating expression levels proteins. This study aims to investigate epigenetic modifications regulating disulfidptosis tumor explore possible triggering factors development microscopic point view, provide potential targets therapy perspective antitumor drugs combination therapies.

Language: Английский

---

Breast cancer: pathogenesis and treatments

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 18, 2025

Abstract Breast cancer, characterized by unique epidemiological patterns and significant heterogeneity, remains one of the leading causes malignancy-related deaths in women. The increasingly nuanced molecular subtypes breast cancer have enhanced comprehension precision treatment this disease. mechanisms tumorigenesis progression been central to scientific research, with investigations spanning various perspectives such as tumor stemness, intra-tumoral microbiota, circadian rhythms. Technological advancements, particularly those integrated artificial intelligence, significantly improved accuracy detection diagnosis. emergence novel therapeutic concepts drugs represents a paradigm shift towards personalized medicine. Evidence suggests that optimal diagnosis models tailored individual patient risk expected are crucial, supporting era oncology for cancer. Despite rapid advancements increasing emphasis on clinical comprehensive update summary panoramic knowledge related disease needed. In review, we provide thorough overview global status including its epidemiology, factors, pathophysiology, subtyping. Additionally, elaborate latest research into contributing progression, emerging strategies, long-term management. This review offers valuable insights Cancer Research, thereby facilitating future progress both basic application.

Language: Английский

---

Gaudichaudione H Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Disulfidptosis via Regulating NRF2‐SLC7A11 Signaling Pathway

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Abstract Gaudichaudione H (GH) is a naturally occurring small molecular compound derived from Garcinia oligantha Merr . (Clusiaceae), but the full pharmacological functions remain unclear. Herein, potential of GH in disulfidptosis regulation, novel form programmed cell death induced by disulfide stress explored. The omics results indicated that NRF2 signaling could be significantly activated GH. targets are associated with hepatocarcinogenesis and death. Moreover, both glutathione (GSH) metabolism NADP + ‐NADPH affected GH, indicating regulation. It also observed enhanced sensitivity hepatocellular carcinoma (HCC) cells to disulfidptosis, which dependent on activation NRF2‐SLC7A11 pathway. increased levels promoted transcription target gene, SLC7A11, through autophagy‐mediated non‐canonical mechanism. Under condition glucose starvation, GH‐induced upregulation SLC7A11 aggravated uptake cysteine, disturbance GSH synthesis, depletion NADPH, accumulation molecules, ultimately leading formation bonds between different cytoskeleton proteins eventually. Collectively, findings underscore role promoting cancer thereby offering promising avenue for treatment drug‐resistant HCC clinical settings.

Language: Английский

---

Sonodynamic Activated Nanoparticles with Glut1 Inhibitor and Cystine-containing Polymer Stimulate Disulfidptosis for Improved Immunotherapy in Bladder Cancer

Biomaterials, Journal Year: 2025, Volume and Issue: 319, P. 123178 - 123178

Published: Feb. 8, 2025

Language: Английский

---

Molecular landmarks of tumor disulfidptosis across cancer types to promote disulfidptosis-target therapy

Redox Biology, Journal Year: 2023, Volume and Issue: 68, P. 102966 - 102966

Published: Nov. 19, 2023

The mystery about the mechanistic basis of disulfidptosis has recently been unraveled and shows promise as an effective treatment modality for triggering cancer cell death. However, limited understanding role in tumor progression drug sensitivity hindered development disulfidptosis-targeted therapy combinations with other therapeutic strategies. Here, we established a signature model to estimate status approximately 10,000 samples across 33 types revealed its prognostic value. Then, characterized disulfidptosis-associated molecular features identified various alterations that correlate both drug-resistant drug-sensitive responses anti-tumor drugs. We further showed vast heterogeneity among 760 lines 25 types. experimentally validated score-high are more susceptible glucose starvation-induced compared their counterparts low scores. Finally, investigated impact on response induction may enhance anti-cancer drugs, but some cases, it could also lead resistance cultured cells. Overall, our multi-omics analysis firstly elucidates comprehensive profile disulfidptosis-related alterations, prognosis, potential therapies at pan-cancer level. These findings uncover opportunities utilize multiple sensitivities induced by disulfidptosis, thereby offering practical implications clinical therapy.

Language: Английский

---

Reductive stress in cancer: coming out of the shadows

Trends in cancer, Journal Year: 2023, Volume and Issue: 10(2), P. 103 - 112

Published: Nov. 2, 2023

Language: Английский

---

Emerging role of immunogenic cell death in cancer immunotherapy

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 10, 2024

Cancer immunotherapy, such as immune checkpoint blockade (ICB), has emerged a groundbreaking approach for effective cancer treatment. Despite its considerable potential, clinical studies have indicated that the current response rate to immunotherapy is suboptimal, primarily attributed low immunogenicity in certain types of malignant tumors. Immunogenic cell death (ICD) represents form regulated (RCD) capable enhancing tumor and activating tumor-specific innate adaptive responses immunocompetent hosts. Therefore, gaining deeper understanding ICD evolution crucial developing more therapeutic strategies. This review focuses exclusively on both historical recent discoveries related modes their mechanistic insights, particularly within context immunotherapy. Our findings are also highlighted, revealing mode induction facilitated by atypical interferon (IFN)-stimulated genes (ISGs), including polo-like kinase 2 ( PLK2 ), during hyperactive type I IFN signaling. The concludes discussing potential ICD, with special attention relevance preclinical settings field

Language: Английский

---

Emerging mechanisms and promising approaches in pancreatic cancer metabolism

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(8)

Published: Aug. 1, 2024

Abstract Pancreatic cancer is an aggressive with a poor prognosis. Metabolic abnormalities are one of the hallmarks pancreatic cancer, and cells can adapt to biosynthesis, energy intake, redox needs through metabolic reprogramming tolerate nutrient deficiency hypoxic microenvironments. use glucose, amino acids, lipids as maintain malignant growth. Moreover, they also metabolically interact in tumour microenvironment change cell fate, promote progression, even affect immune responses. Importantly, changes at body level deserve more attention. Basic research clinical trials based on targeted therapy or combination other treatments full swing. A comprehensive in-depth understanding regulation will not only enrich mechanisms disease progression but provide inspiration for new diagnostic therapeutic approaches.

Language: Английский

---