Deciphering breast cancer: from biology to the clinic

Cell, Journal Year: 2023, Volume and Issue: 186(8), P. 1708 - 1728

Published: March 16, 2023

Language: Английский

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Cellular functions of cGAS-STING signaling

Trends in Cell Biology, Journal Year: 2022, Volume and Issue: 33(8), P. 630 - 648

Published: Nov. 24, 2022

Language: Английский

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Mechanisms driving the immunoregulatory function of cancer cells

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(4), P. 193 - 215

Published: Jan. 30, 2023

Language: Английский

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Non-cell-autonomous cancer progression from chromosomal instability

Nature, Journal Year: 2023, Volume and Issue: 620(7976), P. 1080 - 1088

Published: Aug. 23, 2023

Abstract Chromosomal instability (CIN) is a driver of cancer metastasis 1–4 , yet the extent to which this effect depends on immune system remains unknown. Using ContactTracing—a newly developed, validated and benchmarked tool infer nature conditional dependence cell–cell interactions from single-cell transcriptomic data—we show that CIN-induced chronic activation cGAS–STING pathway promotes downstream signal re-wiring in cells, leading pro-metastatic tumour microenvironment. This manifested by type I interferon tachyphylaxis selectively STING corresponding increase cell-derived endoplasmic reticulum (ER) stress response. Reversal CIN, depletion cell or inhibition ER response signalling abrogates CIN-dependent effects microenvironment suppresses competent, but not severely compromised, settings. Treatment with inhibitors reduces CIN-driven melanoma, breast colorectal cancers manner dependent cell-intrinsic STING. Finally, we CIN pervasive cGAS micronuclei are associated signalling, suppression human triple-negative cancer, highlighting viable strategy identify therapeutically intervene tumours spurred inflammation.

Language: Английский

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STING inhibits the reactivation of dormant metastasis in lung adenocarcinoma

Nature, Journal Year: 2023, Volume and Issue: 616(7958), P. 806 - 813

Published: March 29, 2023

Language: Английский

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Specific activation of cGAS-STING pathway by nanotherapeutics-mediated ferroptosis evoked endogenous signaling for boosting systemic tumor immunotherapy

Science Bulletin, Journal Year: 2023, Volume and Issue: 68(6), P. 622 - 636

Published: Feb. 22, 2023

Language: Английский

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Targeting cytokine and chemokine signaling pathways for cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: July 22, 2024

Abstract Cytokines are critical in regulating immune responses and cellular behavior, playing dual roles both normal physiology the pathology of diseases such as cancer. These molecules, including interleukins, interferons, tumor necrosis factors, chemokines, growth factors like TGF-β, VEGF, EGF, can promote or inhibit growth, influence microenvironment, impact efficacy cancer treatments. Recent advances targeting these pathways have shown promising therapeutic potential, offering new strategies to modulate system, progression, overcome resistance conventional therapies. In this review, we summarized current understanding implications cytokine chemokine signaling By exploring molecules biology response, highlighted development novel agents aimed at modulating combat The review elaborated on nature cytokines promoters suppressors tumorigenesis, depending context, discussed challenges opportunities presents for intervention. We also examined latest advancements targeted therapies, monoclonal antibodies, bispecific receptor inhibitors, fusion proteins, engineered variants, their metastasis, microenvironment. Additionally, evaluated potential combining therapies with other treatment modalities improve patient outcomes. Besides, focused ongoing research clinical trials that pivotal advancing our application cytokine- chemokine-targeted patients.

Language: Английский

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Harnessing innate immune pathways for therapeutic advancement in cancer

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 25, 2024

Abstract The innate immune pathway is receiving increasing attention in cancer therapy. This ubiquitous across various cell types, not only cells but also adaptive cells, tumor and stromal cells. Agonists targeting the have shown profound changes microenvironment (TME) improved prognosis preclinical studies. However, to date, clinical success of drugs remains limited. Interestingly, recent studies that activation can paradoxically promote progression. uncertainty surrounding therapeutic effectiveness targeted for a critical issue needs immediate investigation. In this review, we observe role demonstrates heterogeneity, linked development stage, status, specific types. We propose within TME, exhibits multidimensional diversity. diversity fundamentally rooted cellular heterogeneity manifested as variety signaling networks. pro-tumor effect essentially reflects suppression classical pathways potential alternative pathways. Refining our understanding tumor’s network employing appropriate strategies enhance ability harness anti-tumor ultimately bridge gap from application.

Language: Английский

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Current understanding of the cGAS-STING signaling pathway: Structure, regulatory mechanisms, and related diseases

动物学研究, Journal Year: 2023, Volume and Issue: 44(1), P. 183 - 218

Published: Jan. 1, 2023

The innate immune system protects the host from external pathogens and internal damage in various ways. cGAS-STING signaling pathway, comprised of cyclic GMP-AMP synthase (cGAS), stimulator interferon genes (STING), downstream adaptors, plays an essential role protective defense against microbial DNA damaged-associated is responsible for immune-related diseases. After binding with DNA, cytosolic cGAS undergoes conformational change DNA-linked liquid-liquid phase separation to produce 2'3'-cGAMP activation endoplasmic reticulum (ER)-localized STING. However, further studies revealed that predominantly expressed nucleus strictly tethered chromatin prevent nuclear functions differently cytosolic-localized cGAS. Detailed delineation this including its structure, signaling, regulatory mechanisms, great significance fully understand diversity will be benefit treatment inflammatory diseases cancer. Here, we review recent progress on above-mentioned perspectives pathway discuss new avenues study.

Language: Английский

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The two sides of chromosomal instability: drivers and brakes in cancer

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 29, 2024

Abstract Chromosomal instability (CIN) is a hallmark of cancer and associated with tumor cell malignancy. CIN triggers chain reaction in cells leading to chromosomal abnormalities, including deviations from the normal chromosome number or structural changes chromosomes. arises errors DNA replication segregation during division, formation abnormal and/or structure Errors result licensing as well stress, such double-strand breaks stalled forks; meanwhile, stem defects machinery, centrosome amplification, erroneous microtubule–kinetochore attachments, spindle assembly checkpoint, defective sister chromatids cohesion. In cells, deleterious damage, proteotoxic metabolic alteration, cycle arrest, senescence. Paradoxically, despite these negative consequences, one hallmarks found over 90% solid tumors blood cancers. Furthermore, could endow enhanced adaptation capabilities due increased intratumor heterogeneity, thereby facilitating adaptive resistance therapies; however, excessive induce death, “just-right” model for tumors. Elucidating complex nature crucial understanding dynamics tumorigenesis developing effective anti-tumor treatments. This review provides an overview causes consequences CIN, paradox phenomenon that continues perplex researchers. Finally, this explores potential CIN-based therapy.

Language: Английский

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