Histone lactylation regulates cancer progression by reshaping the tumor microenvironment

Qu, Junxing; Li, Peizhi; Sun, Zhiheng

doi:10.3389/fimmu.2023.1284344

Cited by 14 publications

(5 citation statements)

References 118 publications

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“…In 2019, Zhang et al [128] identified histone lysine lactylation (lactyl-amide conjugation) and protein lactylation as an effect of lactate accumulation able to introduce epigenetic changes and modify post-translational characteristics of some proteins. Since then, it was found that lactylation participates in many pro-tumoral hallmarks [129][130][131][132][133][134][135][136][137][138][139]. Interestingly, DCA is one of the drugs that can decrease/inhibit lactylation.…”

Section: Mechanism Of Action Of Dcamentioning

confidence: 99%

Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts

Koltai,

Fliegel

2024

Preprint

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Rarely has a chemical elicited as much controversy as has dichloroacetate (DCA). DCA was initially considered a dangerous toxic industrial waste product. Then it was a potential treatment for lactic acidosis. However, the main controversies started in 2008 when DCA was found to have anti-cancer effects in experimental animals. These publications showed contradictory results in vivo and in vitro, so that a thorough consideration of this compound in cancer is merited. Despite 50 years of experimentation, DCA’s future in therapeutics is uncertain. Without adequate clinical trials and lack of health authorities’ approval, DCA has been introduced in off -label cancer treatments in alternative medicine clinics in Canada, Germany, and other European countries. The lack of well-planned clinical trials and its use by people without medical training has discouraged consideration by the scientific community. There are limited thorough clinical studies of DCA, and many publications are individual case reports. Case reports of DCA benefits against cancer have been increasing recently. Furthermore, it has been shown that DCA synergizes with conventional treatments and other repurposable drugs. Beyond the classic DCA target, pyruvate dehydrogenase kinase, new target molecules have also been recently discovered. These findings have renewed interest in DCA. This paper explores whether existing evidence justifies further research on DCA for cancer treatment and it explores the role DCA may play in oncology treatment.

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Section: Mechanism Of Action Of Dcamentioning

confidence: 99%

Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts

Koltai,

Fliegel

2024

Preprint

View full text Add to dashboard Cite

show abstract

“…In 2019, Zhang et al [ 128 ] identified histone lysine lactylation (lactyl-amide conjugation) and protein lactylation as effects of lactate accumulation that are able to introduce epigenetic changes and modify the post-translational characteristics of some proteins. Since then, it was found that lactylation participates in many protumoral hallmarks [ 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 ]. Interestingly, DCA is one of the drugs that can decrease/inhibit lactylation.…”

Section: The Pdh Complexmentioning

confidence: 99%

Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts

Koltai,

Fliegel

2024

Pharmaceuticals

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Rarely has a chemical elicited as much controversy as dichloroacetate (DCA). DCA was initially considered a dangerous toxic industrial waste product, then a potential treatment for lactic acidosis. However, the main controversies started in 2008 when DCA was found to have anti-cancer effects on experimental animals. These publications showed contradictory results in vivo and in vitro such that a thorough consideration of this compound’s in cancer is merited. Despite 50 years of experimentation, DCA’s future in therapeutics is uncertain. Without adequate clinical trials and health authorities’ approval, DCA has been introduced in off-label cancer treatments in alternative medicine clinics in Canada, Germany, and other European countries. The lack of well-planned clinical trials and its use by people without medical training has discouraged consideration by the scientific community. There are few thorough clinical studies of DCA, and many publications are individual case reports. Case reports of DCA’s benefits against cancer have been increasing recently. Furthermore, it has been shown that DCA synergizes with conventional treatments and other repurposable drugs. Beyond the classic DCA target, pyruvate dehydrogenase kinase, new target molecules have also been recently discovered. These findings have renewed interest in DCA. This paper explores whether existing evidence justifies further research on DCA for cancer treatment and it explores the role DCA may play in it.

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“…The activity of epigenetic modulators requires cellular metabolites; thus, understanding the interplay between epigenetics and metabolism in disease contexts is essential. For example, the tumor microenvironment in cancer vastly differs in its metabolic makeup compared with surrounding normal tissue ( Qu et al 2023 ), which could have a profound impact on the epigenetic modulators as a whole or selectively. Additionally, attention on RNA epigenetics and its role in stress, aging, metabolism, and immunology is a young but exciting field that will open future opportunities for discovery.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Epigenetic modulators provide a path to understanding disease and therapeutic opportunity

Honer,

Ferman,

Gray

et al. 2024

Genes Dev.

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The discovery of epigenetic modulators (writers, erasers, readers, and remodelers) has shed light on previously underappreciated biological mechanisms that promote diseases. With these insights, novel biomarkers and innovative combination therapies can be used to address challenging and difficult to treat disease states. This review highlights key mechanisms that epigenetic writers, erasers, readers, and remodelers control, as well as their connection with disease states and recent advances in associated epigenetic therapies.

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Histone lactylation regulates cancer progression by reshaping the tumor microenvironment

Cited by 14 publications

References 118 publications

Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts

Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts

Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts

Epigenetic modulators provide a path to understanding disease and therapeutic opportunity

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