Deciphering the interplay of histone post-translational modifications in cancer: Co-targeting histone modulators for precision therapy.

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.

Decoding cell death signalling: Impact on the response of breast cancer cells to approved therapies.

Breast cancer is a principal cause of cancer-related mortality in female worldwide. While many approved therapies have shown promising outcomes in treating breast cancer, understanding the intricate signalling pathways controlling cell death is crucial for optimizing the treatment outcome. A growing body of evidence has unveiled the aberrations in multiple cell death pathways across diverse cancer types, highlighting these pathways as appealing targets for therapeutic interventions. In this review, we provide a comprehensive overview of the current state of knowledge on the cell death signalling mechanisms with a particular focus on their impact on the response of breast cancer cells to approved therapies. Additionally, we discuss the potentials of combination therapies that exploit the synergy between approved drugs and therapeutic agents targeting modulators of cell death pathways.