A framework for the development of effective anti-metastatic agents

Nature Reviews Clinical Oncology, Journal Year: 2018, Volume and Issue: 16(3), P. 185 - 204

Published: Dec. 4, 2018

Abstract Most cancer-related deaths are a result of metastasis, and thus the importance this process as target therapy cannot be understated. By asking ‘how can we effectively treat cancer?’, do not capture complexity disease encompassing >200 different cancer types — many consisting multiple subtypes with considerable intratumoural heterogeneity, which in variable responses to specific therapy. Moreover, have much less information on pathophysiological characteristics metastases than is available for primary tumour. disseminated tumour cells that arrive distant tissues, surrounded by unfamiliar foreign microenvironment, likely die; however, those survive generate metastatic tumours markedly biology from To metastasis effectively, must inhibit fundamental processes develop preclinical clinical strategies rely responses. address crucial issue, Cancer Research UK Therapeutics CRC Australia formed Metastasis Working Group representatives not-for-profit, academic, government, industry regulatory bodies order recommendations how tackle challenges associated treating (micro)metastatic disease. Herein, describe identified well proposed approaches discovering developing anticancer agents designed specifically prevent or delay outgrowth cancer.

Language: Английский

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Epigenetic Silencing of CDR1as Drives IGF2BP3-Mediated Melanoma Invasion and Metastasis

Cancer Cell, Journal Year: 2020, Volume and Issue: 37(1), P. 55 - 70.e15

Published: Jan. 1, 2020

Language: Английский

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The influence of diet on anti-cancer immune responsiveness

Journal of Translational Medicine, Journal Year: 2018, Volume and Issue: 16(1)

Published: March 20, 2018

Immunotherapy has matured into standard treatment for several cancers, but much remains to be done extend the reach of its effectiveness particularly cancers that are resistant within each indication. This review proposes nutrition can affect and potentially enhance immune response against cancer. The general mechanisms link nutritional principles function may influence anticancer immunotherapy examined. represents also premise a research project aimed at identifying best diet enhancement tumours (D.I.E.T project). Particular attention is turned gut microbiota impact composition on system. Also, dietary patterns effecting discussed including value adhering healthy diets such as Mediterranean, Veg, Japanese, or Microbiota-regulating diet, very low ketogenic which have been demonstrated lower risk developing reduce mortality associated with them. Finally, supplements, omega-3 polyphenols, potential approaches could benefit lifestyle habits in context immunotherapy.

Language: Английский

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Promoter DNA Hypermethylation and Paradoxical Gene Activation

Trends in cancer, Journal Year: 2020, Volume and Issue: 6(5), P. 392 - 406

Published: March 9, 2020

Language: Английский

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Targeting DNA Methylation and EZH2 Activity to Overcome Melanoma Resistance to Immunotherapy

Trends in Immunology, Journal Year: 2019, Volume and Issue: 40(4), P. 328 - 344

Published: March 7, 2019

Methylation of DNA at CpG sites is the most common and stable epigenetic changes in cancer. Hypermethylation acts to limit immune checkpoint blockade immunotherapy by inhibiting endogenous interferon responses needed for recognition cancer cells. By contrast, global hypomethylation results expression programmed death ligand 1 (PD-L1) inhibitory cytokines, accompanied epithelial-mesenchymal that can contribute immunosuppression. The drivers these contrasting methylation states are not well understood. also plays a key role cytotoxic T cell 'exhaustion' associated with tumor progression. We present an updated exploratory analysis how may define patient subgroups be targeted develop tailored treatment combinations help improve outcomes.

Language: Английский

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The Roles of Human DNA Methyltransferases and Their Isoforms in Shaping the Epigenome

Genes, Journal Year: 2019, Volume and Issue: 10(2), P. 172 - 172

Published: Feb. 23, 2019

A DNA sequence is the hard copy of human genome and it a driving force in determining physiological processes an organism. Concurrently, chemical modification its related histone proteins dynamically involved regulating diseases, which overall constitutes epigenome network. Among various forms epigenetic modifications, methylation at C-5 position cytosine cytosine⁻guanine (CpG) dinucleotide one most well studied modifications. methyltransferases (DNMTs) are family enzymes generating maintaining CpG across genome. In mammalian systems, performed by DNMT1 DNMT3s (DNMT3A 3B). predominantly maintenance during cell division, while establishing de novo both embryonic somatic cells. general, all DNMTs require accessory proteins, such as ubiquitin-like containing plant homeodomain (PHD) really interesting new gene (RING) finger domain 1 (UHRF1) or DNMT3-like (DNMT3L), for their biological function. This review mainly focuses on role DNMT3B isoforms methylation, especially with respect to protein.

Language: Английский

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KMT2C deficiency promotes small cell lung cancer metastasis through DNMT3A-mediated epigenetic reprogramming

Nature Cancer, Journal Year: 2022, Volume and Issue: 3(6), P. 753 - 767

Published: April 21, 2022

Language: Английский

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Transient loss of Polycomb components induces an epigenetic cancer fate

Nature, Journal Year: 2024, Volume and Issue: 629(8012), P. 688 - 696

Published: April 24, 2024

Although cancer initiation and progression are generally associated with the accumulation of somatic mutations

Language: Английский

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Unraveling the tumor microenvironment: Insights into cancer metastasis and therapeutic strategies

Cancer Letters, Journal Year: 2024, Volume and Issue: 591, P. 216894 - 216894

Published: April 16, 2024

This comprehensive review delves into the pivotal role of tumor microenvironment (TME) in cancer metastasis and therapeutic response, offering fresh insights intricate interplay between cells their surrounding milieu. The TME, a dynamic ecosystem comprising diverse cellular acellular elements, not only fosters progression but also profoundly affects efficacy conventional emerging therapies. Through nuanced exploration, this illuminates multifaceted nature elucidating its capacity to engender drug resistance via mechanisms such as hypoxia, immune evasion, establishment physical barriers delivery. Moreover, it investigates innovative approaches aimed at targeting including stromal reprogramming, modulation, extracellular matrix (ECM)-targeting agents, personalized medicine strategies, highlighting potential augment treatment outcomes. Furthermore, critically evaluates challenges posed by complexity heterogeneity which contribute variable responses potentially unintended consequences. underscores need identify robust biomarkers advance predictive models anticipate outcomes, well advocate for combination therapies that address multiple facets TME. Finally, emphasizes necessity an interdisciplinary approach integration cutting-edge technologies unravel intricacies thereby facilitating development more effective, adaptable, treatments. By providing critical current state TME research implications future oncology, highlights evolving landscape field.

Language: Английский

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Chromosomal instability as a driver of cancer progression

Nature Reviews Genetics, Journal Year: 2024, Volume and Issue: 26(1), P. 31 - 46

Published: July 29, 2024

Language: Английский

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