Lysine Acetylation, Cancer Hallmarks and Emerging Onco-Therapeutic Opportunities

SIMPLE SUMMARY: Several histone deacetylase inhibitors have been approved by FDA for cancer treatment. Intensive efforts have been devoted to enhancing its anti-cancer efficacy by combining it with various other agents. Yet, no guideline is available to assist in the choice of candidate drugs for combination towards optimal solutions for different clinical problems. Thus, it is imperative to characterize the primary cancer hallmarks that lysine acetylation is associated with and gain knowledge on the key cancer features that each combinatorial onco-therapeutic modality targets to aid in the combinatorial onco-therapeutic design. Cold atmospheric plasma represents an emerging anti-cancer modality via manipulating cellular redox level and has been demonstrated to selectively target several cancer hallmarks. This review aims to delineate the intrinsic connections between lysine acetylation and cancer properties, and forecast opportunities histone deacetylase inhibitors may have when combined with cold atmospheric plasma as novel precision onco-therapies. ABSTRACT: Acetylation, a reversible epigenetic process, is implicated in many critical cellular regulatory systems including transcriptional regulation, protein structure, activity, stability, and localization. Lysine acetylation is the most prevalent and intensively investigated among the diverse acetylation forms. Owing to the intrinsic connections of acetylation with cell metabolism, acetylation has been associated with metabolic disorders including cancers. Yet, relatively little has been reported on the features of acetylation against the cancer hallmarks, even though this knowledge may help identify appropriate therapeutic strategies or combinatorial modalities for the effective treatment and resolution of malignancies. By examining the available data related to the efficacy of lysine acetylation against tumor cells and elaborating the primary cancer hallmarks and the associated mechanisms to target the specific hallmarks, this review identifies the intrinsic connections between lysine acetylation and cancer hallmarks and proposes novel modalities that can be combined with HDAC inhibitors for cancer treatment with higher efficacy and minimum adverse effects.