Targeting estrogen-regulated system xc− promotes ferroptosis and endocrine sensitivity of ER+ breast cancer

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 20, 2025

Abstract Estrogen receptor positive (ER+) breast cancer accounts for approximately 70% of cases. Endocrine therapies targeting estrogen are the first line ER+ cancer. However, resistance to these occurs in about half patients, leading decreased survival rates. Inducing ferroptosis is a promising therapeutic strategy treatment refractory and malignant cancers including triple-negative Nevertheless, relatively resistant inducers. Here, we uncovered that ERα suppressed Silencing triggered ferroptosis, which was attenuated by inhibitor Ferrostatin-1, enhanced inducer Erastin. Mechanistically, transcriptionally upregulated expression SLC7A11 SLC3A2, two subunits system x c − , one key inhibitory regulator ferroptosis. Overexpression exogenous SLC3A2 able mitigate induced inhibition. Moreover, levels were elevated endocrine-resistant cells tumors. Importantly, Sorafenib or Imidazole ketone erastin effectively inhibited growth tamoxifen-resistant vitro vivo. In conclusion, our data reveal estrogen-regulated enhances cancer, offering novel option patients with particularly those endocrine resistance.

Language: Английский

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Advances in Ferroptosis Research: A Comprehensive Review of Mechanism Exploration, Drug Development, and Disease Treatment

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(3), P. 334 - 334

Published: Feb. 26, 2025

In recent years, ferroptosis, as an emerging modality of programmed cell death, has captured significant attention within the scientific community. This comprehensive review meticulously canvasses pertinent literature past few spanning multiple facets. It delves into intricate mechanisms underpinning tracks evolution its inducers and inhibitors, dissects roles in a diverse array diseases, well resultant therapeutic implications. A profound exploration is conducted functional ferroptosis-related molecules, intracellular pathways, metabolic cascades, signaling transduction routes. Novel ferroptosis inhibitors are introduced detail, covering their design blueprints, synthetic methodologies, bioactivity profiles. Moreover, exhaustive account provided regarding involvement malignancies, neurodegenerative disorders, cardiovascular ailments, other pathologies. By highlighting pivotal status potential regimens various this aspires to furnish thorough reference framework for future investigations clinical translations domain.

Language: Английский

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Molecular Mechanisms and Therapeutic Strategies to Overcome Resistance to Endocrine Therapy and CDK4/6 Inhibitors in Advanced ER+/HER2− Breast Cancer

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3438 - 3438

Published: April 7, 2025

Approximately 70-80% of breast cancers are estrogen receptor-positive (ER+), with 65% these cases also being progesterone (ER+PR+). In most ER+ advanced cancer, endocrine therapy (ET) serves as the first-line treatment, utilizing various drugs that inhibit ER signaling. These include tamoxifen, a selective receptor modulator (SERM); fulvestrant, degrader (SERD); and aromatase inhibitors (AIs), which block synthesis. However, intrinsic or acquired hormone resistance eventually develops, leading to disease progression. The combination ET cyclin-dependent kinase 4 6 (CDK4/6is) has been shown significantly increase progression-free survival (PFS) and, in some cases, overall (OS). CDK4/6is works by arresting cell cycle G1 phase, preventing DNA synthesis, enhancing efficacy ET. This review highlights key mechanisms ET, whether used alone biological agents, well emerging therapeutic strategies aimed at overcoming resistance. Addressing remains work progress, near future, better patient selection for different approaches is expected through identification more precise genetic markers. particular, liquid biopsy may provide real-time portrait disease, offering insights into driving cancer

Language: Английский

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Ferroptosis in Cancer: Mechanism and Therapeutic Potential

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3852 - 3852

Published: April 18, 2025

Cancer drug resistance occurs when cancer cells evade cell death following treatment with chemotherapy, radiation therapy, and targeted therapies. This is often linked to the reprogramming of programmed (PCD) pathways, allowing survive drug-induced stress. However, certain anticancer therapies, combined specific agents or inhibitors, can induce ferroptosis—a form driven by iron-dependent lipid peroxidation. Currently, extensive preclinical clinical research underway investigate molecular, cellular, tissue-specific mechanisms underlying ferroptosis, goal identifying strategies overcome in cancers unresponsive conventional PCD pathways. By harnessing be compelled undergo peroxidation-induced death, potentially improving therapeutic outcomes patients cancer. short review aims enhance understanding ferroptosis inducers therapy stimulate further into ferroptosis-based approaches for more effective treatment.

Language: Английский

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Targeting ferroptosis reveals a new strategy for breast cancer treatment: a bibliometric study

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 19, 2024

Studies exploring the role of ferroptosis in pathogenesis breast cancer have proliferated over past decade, especially 2023, with a staggering 217 publications related studies. However, there are still significant gaps comprehensive scientometric analysis and mapping scientific studies, terms temporal study area tracking, principal investigators, emergence new hotspots. This aims to summarize development latest research results on ferroptosis-targeted treatment use bibliometric methods draw visual map explore future trends. On May 11, 2024, this updated progress 11 years by retrieving data from January 1, 2014, Web Science database. In research, many software including VOSviewer, chorddiag R Language Pack, Scimago Graphica, Citespace 6.3.R1, Cluster Profiler, enrichplot, ggplot2 Cytoscape, STRING online platform used make in-depth visualization measurement results. Statistical these showed that China accounted for 74.43% total publications, highlighting China's dominant relationship between cancer. Several institutions, Sun Yat-sen University, Zhejiang Shanghai Jiao Tong achieved impressive Efferth, Thomas is most prominent author field has highest number subfield oncology. clearly shows plays crucial triple-negative cancer, hepatocellular carcinoma, glioma, leukemia, mitochondrial disease, lymphoma, bladder tumors, lung adenocarcinoma, esophageal tumors. provides evaluation deepens our understanding current status targeting treating Thus, it helps researchers fields directions comprehensively extracting important information

Language: Английский

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