Deciphering the interplay of histone post-translational modifications in cancer: Co-targeting histone modulators for precision therapy.
Life Sci
; 346: 122639, 2024 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-38615747
ABSTRACT
Chromatin undergoes dynamic regulation through reversible histone post-translational modifications (PTMs), orchestrated by "writers," "erasers," and "readers" enzymes. Dysregulation of these histone modulators is well implicated in shaping the cancer epigenome and providing avenues for precision therapies. The approval of six drugs for cancer therapy targeting histone modulators, along with the ongoing clinical trials of numerous candidates, represents a significant advancement in the field of precision medicine. Recently, it became apparent that histone PTMs act together in a coordinated manner to control gene expression. The intricate crosstalk of histone PTMs has been reported to be dysregulated in cancer, thus emerging as a critical factor in the complex landscape of cancer development. This formed the foundation of the swift emergence of co-targeting different histone modulators as a new strategy in cancer therapy. This review dissects how histone PTMs, encompassing acetylation, phosphorylation, methylation, SUMOylation and ubiquitination, collaboratively influence the chromatin states and impact cellular processes. Furthermore, we explore the significance of histone modification crosstalk in cancer and discuss the potential of targeting histone modification crosstalk in cancer management. Moreover, we underscore the significant strides made in developing dual epigenetic inhibitors, which hold promise as emerging candidates for effective cancer therapy.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Histonas
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Procesamiento Proteico-Postraduccional
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Medicina de Precisión
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Neoplasias
Límite:
Animals
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Humans
Idioma:
En
Revista:
Life Sci
Año:
2024
Tipo del documento:
Article
País de afiliación:
Emiratos Árabes Unidos