Targeting HER2-positive breast cancer: advances and future directions

Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 22(2), P. 101 - 126

Published: Nov. 7, 2022

Language: Английский

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NF-κB in biology and targeted therapy: new insights and translational implications

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

Published: March 4, 2024

Abstract NF-κB signaling has been discovered for nearly 40 years. Initially, was identified as a pivotal pathway in mediating inflammatory responses. However, with extensive and in-depth investigations, researchers have that its role can be expanded to variety of mechanisms, biological processes, human diseases, treatment options. In this review, we first scrutinize the research process signaling, summarize composition, activation, regulatory mechanism signaling. We investigate interaction other important pathways, including PI3K/AKT, MAPK, JAK-STAT, TGF-β, Wnt, Notch, Hedgehog, TLR The physiological pathological states well intricate involvement inflammation, immune regulation, tumor microenvironment, are also explicated. Additionally, illustrate how is involved cancers, autoimmune cardiovascular metabolic neurological COVID-19. Further, discuss therapeutic approaches targeting IKK inhibitors, monoclonal antibodies, proteasome nuclear translocation DNA binding TKIs, non-coding RNAs, immunotherapy, CAR-T. Finally, provide an outlook field hope present stereoscopic, comprehensive will inform future clinical practice.

Language: Английский

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Metastasis

Cell, Journal Year: 2023, Volume and Issue: 186(8), P. 1564 - 1579

Published: April 1, 2023

Language: Английский

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Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Nov. 1, 2022

Abstract Exosomes are well-known key mediators of intercellular communication and contribute to various physiological pathological processes. Their biogenesis involves four steps, including cargo sorting, MVB formation maturation, transport MVBs, fusion with the plasma membrane. Each process is modulated through competition or coordination multiple mechanisms, whereby diverse repertoires molecular cargos sorted into distinct subpopulations exosomes, resulting in high heterogeneity exosomes. Intriguingly, cancer cells exploit strategies, such as aberrant gene expression, posttranslational modifications, altered signaling pathways, regulate biogenesis, composition, eventually functions exosomes promote progression. Therefore, exosome biogenesis-targeted therapy being actively explored. In this review, we systematically summarize recent progress understanding machinery how it regulated context cancer. particular, highlight pharmacological targeting a promising therapeutic strategy.

Language: Английский

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Targeting the gut and tumor microbiota in cancer

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(4), P. 690 - 703

Published: April 1, 2022

Language: Английский

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Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions

Cell, Journal Year: 2022, Volume and Issue: 185(20), P. 3789 - 3806.e17

Published: Sept. 1, 2022

Cancer-microbe associations have been explored for centuries, but cancer-associated fungi rarely examined. Here, we comprehensively characterize the cancer mycobiome within 17,401 patient tissue, blood, and plasma samples across 35 types in four independent cohorts. We report fungal DNA cells at low abundances many major human cancers, with differences community compositions that differ among types, even when accounting technical background. Fungal histological staining of tissue microarrays supported intratumoral presence frequent spatial association macrophages. Comparing communities matched bacteriomes immunomes revealed co-occurring bi-domain ecologies, often permissive, rather than competitive, microenvironments distinct immune responses. Clinically focused assessments suggested prognostic diagnostic capacities mycobiomes, stage I synergistic predictive performance bacteriomes.

Language: Английский

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Copper metabolism in cell death and autophagy

Autophagy, Journal Year: 2023, Volume and Issue: 19(8), P. 2175 - 2195

Published: April 14, 2023

Copper is an essential trace element in biological systems, maintaining the activity of enzymes and function transcription factors. However, at high concentrations, copper ions show increased toxicity by inducing regulated cell death, such as apoptosis, paraptosis, pyroptosis, ferroptosis, cuproptosis. Furthermore, can trigger macroautophagy/autophagy, a lysosome-dependent degradation pathway that plays dual role regulating survival or death fate cells under various stress conditions. Pathologically, impaired metabolism due to environmental genetic causes implicated variety human diseases, rare Wilson disease common cancers. Therapeutically, copper-based compounds are potential chemotherapeutic agents be used alone combination with other drugs approaches treat cancer. Here, we review progress made understanding metabolic processes their impact on regulation autophagy. This knowledge may help design future clinical tools improve cancer diagnosis treatment.

Language: Английский

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BCL-2 protein family: attractive targets for cancer therapy

APOPTOSIS, Journal Year: 2022, Volume and Issue: 28(1-2), P. 20 - 38

Published: Nov. 7, 2022

Acquired resistance to cell death is a hallmark of cancer. The BCL-2 protein family members play important roles in controlling apoptotic death. Abnormal over-expression pro-survival or abnormal reduction pro-apoptotic proteins, both resulting the inhibition apoptosis, are frequently detected diverse malignancies. critical role and proteins regulation apoptosis makes them attractive targets for development agents treatment This review describes various normal organismal function how defects control promote therapy Finally, we discuss inhibitors termed BH3-mimetic drugs, as novel cancer therapy.

Language: Английский

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RNA splicing dysregulation and the hallmarks of cancer

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(3), P. 135 - 155

Published: Jan. 10, 2023

Language: Английский

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Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 19, 2023

Abstract The Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved mechanism transmembrane transduction that enables cells to communicate with the exterior environment. Various cytokines, interferons, growth factors, other specific molecules activate JAK-STAT signaling drive a series physiological pathological processes, including proliferation, metabolism, immune response, inflammation, malignancy. Dysregulated related genetic mutations are strongly associated activation cancer progression. Insights into structures functions have led development approval diverse drugs for clinical treatment diseases. Currently, been developed mainly target commonly divided three subtypes: cytokine or receptor antibodies, JAK inhibitors, STAT inhibitors. And novel agents also continue be tested in preclinical studies. effectiveness safety each kind drug warrant further scientific trials before put being applications. Here, we review current understanding fundamental composition function pathway. We discuss advancements JAK-STAT–related pathogenic mechanisms; targeted therapies various diseases, especially disorders, cancers; newly inhibitors; challenges directions field.

Language: Английский

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