Epigenetics and cancer – A dependence relationship

Epigenetics refers to nonpermanent modifications in the nucleic acids and histones of DNA molecules^[1]. The most common epigenetic modifications include the methylation of the promoter region of several genes and the acetylation of several histones, although there are many others^[2]. These modifications can lead to aberrant expression of several genes, leading to carcinogenesis. A characteristic paradigm of this procedure is the silencing of tumor-suppressor gene promoters associated with cancer development^[3]. Epigenetic modifications can also lead to the inability of T lymphocytes to effectively recognize cancer cells, because of dysregulation of antigen presentation in the latter^[4]. Moreover, a promotion of the production of pro-inflammatory cytokines can be directed via epigenetic modification mechanisms in specific genes^[5]. Methylation of the promoter region of PD-L1 gene causes an overexpression of PD-L1 in prostate cancer and glioblastoma patients, leading to a more aggressive disease prognosis^{[6, 7]}. In addition, the methylation of the promoter region of several genes (e.g., SOX-17, Wif-1, RASSF1A) can lead to a decrease in progression-free survival (PFS) and overall survival (OS), as well as a decrease in the response to chemotherapy in patients with metastatic gastric adenocarcinoma^{[8, 9]}.

Recently, many epigenetic drugs have been developed, and they can enhance antitumor responses. Histone deacetylase (HDAC) inhibitors and DNA methyltransferase (DNMT) inhibitors are widely used for the epigenetic therapy of several tumors^[2]. Epigenetic drugs seem to improve the responses of immunotherapy agents during cancer therapy. In ovarian cancer mouse models, the combination of azacytidine and an anti-CTLA4 antibody can lead to chemokine increase and tumor growth inhibition^[10]. DNMT inhibitors can make cancer cells behave like being virus-infected, a phenomenon called ’viral mimicry‘, leading to interferon pathway activation and enhancement of immunotherapy^[11]. A novel EZH2 inhibitor (tazemetostat) has been developed recently for the treatment of epithelioid sarcoma and is the first histone ’writer‘ inhibitor^[12]. In recent years, an increasing number of epigenetic drugs have been approved for the epigenetic therapy of cancer and their combination with immunotherapy agents will lead to robust antitumor responses.

In the current issue of the journal, articles report on some very interesting areas of research, including the prognostic significance of cell-free DNA in gastric cancer^[13], the relationship between sialic acids and cancer^[14], the development of bioflavonoid-containing chemotherapy delivery systems^[15], and more. We believe the articles will be of great interest and will provide readers the opportunity to connect with novel areas of cancer diagnosis and therapy.