Table 5 New treatment strategies in breast cancer
From: The role of epigenetic modifications in drug resistance and treatment of breast cancer
New/future treatment strategies | |||
|---|---|---|---|
| Â | Therapy | Mechanisms of action | References |
Biological agents | DNA methyltransferases (DNMTi) (e.g., azacitidine and decitabine) | Re-expression of MHC molecules, tumor antigens, and changing cytokine production Re-expression of endogenous ERα and PRs Reversing MHC1 gene promoter methylation | |
Histone de-acetylation inhibitors (HDACi) ( e.g., vorinostat, romidepsin, panobinostat, and belinostat) | Increasing the expression of MCH molecules on tumor cells Activation of the process of regulatory T cells Increasing NK cell activity Trapping cell cycle in G1 and G2 phase | ||
LSD1 inhibitors (e.g., TCP, ORY-1001, GSK-2879552, IMG-7289, INCB059872, CC-90011, and ORY-2001) | Reprogramming tumor-associated macrophages into M1 | ||
Histone methyltransferase inhibitors (HMTis) | Suppressing EZH2 Increasing MDSCs in the tumor microenvironment | [101] | |
Synthetic agents | BET inhibitors (e.g., I BET 151(GSK1210151A), I-BET 762 (GSK525762), OTX-015, TEN-010, CPI-203, and CPI-0610.) | Diminishing NF-κB activity, cytokine generation, and PD-L1 expression Suppressing BATF | |
Cell therapy | Estrogen receptor modulators (e.g., tamoxifen and fulvestrant) and aromatase inhibitors (e.g., anastrozole, letrozole, and exemestane) | Trapping cell cycle in G0 and G1 phase Competing with 17β-estradiol (E2) at the receptor site Blocking the enzyme aromatase, thereby reducing the levels of E2, E1, and E1S both in the periphery and in the mammary tissue | |
Monoclonal antibodies (e.g., trastuzumab and pertuzumab) | Inhibiting HER1-HER2 dimerization Enhancing ADCC reaction | [93] | |
Combinational therapy | Tyrosine kinase inhibitors (TKIs) (e.g., lapatinib and neratinib) | Reversibly binding to the cytoplasmic ATP-binding sites of EGFR/HER1 and HER2 receptors, thereby blocking tyrosine kinase phosphorylation | [126] |
Epigenetic therapy | Immunotherapy (e.g., atezolizumab and pembrolizumab) | Agglutination of tumor cells, leading to phagocytosis Immobilization of tumor cells culminate in inhibiting tumor invasion and spreading Phagocytosis, stemming from binding to Fc receptor on macrophages, so-called opsonization Cytotoxicity via NK cells destroying tumor cells Tumor lysis phagocytosis by activation of the complement system Neutralization of active substances | |