Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic School of Medicine & The Mayo Clinic Medical Scientist Training Program, Mayo Clinic, Rochester, MN 55905, USA.
Pharmacogenomics. 2019 Nov;20(16):1151-1157. doi: 10.2217/pgs-2019-0078.
Triple-negative breast cancer (TNBC) accounts for 15-20% of all invasive breast cancers and tends to have aggressive histological features and poor clinical outcomes. Unlike, estrogen receptor- or HER2-positive diseases, TNBC patients currently lack the US FDA-approved targeted therapies. DNA methylation is a critical mechanism of epigenetic modification. It is well known that aberrant DNA methylation contributes to the malignant transformation of cells by silencing critical tumor suppressor genes. DNA methyltransferase inhibitors reactivate silenced tumor suppressor genes and result in tumor growth arrest, with therapeutic effects observed in patients with hematologic malignancies. The antitumor effect of these DNA methyltransferase inhibitors has also been explored in solid tumors, especially in TNBC that currently lacks targeted therapies.
三阴性乳腺癌（TNBC）占所有浸润性乳腺癌的 15-20%，往往具有侵袭性的组织学特征和较差的临床结局。与雌激素受体阳性或 HER2 阳性疾病不同，目前 TNBC 患者缺乏美国食品和药物管理局 (FDA) 批准的靶向治疗药物。DNA 甲基化是一种关键的表观遗传修饰机制。众所周知，异常的 DNA 甲基化通过沉默关键的肿瘤抑制基因导致细胞的恶性转化。DNA 甲基转移酶抑制剂可重新激活沉默的肿瘤抑制基因，导致肿瘤生长停滞，在血液恶性肿瘤患者中观察到治疗效果。这些 DNA 甲基转移酶抑制剂的抗肿瘤作用也在实体肿瘤中得到了探索，特别是在目前缺乏靶向治疗的 TNBC 中。
