Marini Francesca, Giusti Francesca, Brandi Maria Luisa
Department of Experimental and Clinical Biomedical Sciences, University of refereFlorence, Florence, Italy.
F.I.R.M.O. Italian Foundation for the Research on Bone Diseases, Florence, Italy.
Expert Rev Endocrinol Metab. 2021 Nov;16(6):295-307. doi: 10.1080/17446651.2021.1982382. Epub 2021 Sep 23.
Well-differentiated pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of primary tumors of the endocrine pancreas. Dysregulation of chromatin remodeling, gene expression alteration, global DNA hypomethylation of non-coding regions, DNA hypermethylation and silencing of tumor suppressor gene promoters are frequent epigenetic changes in PanNETs. These changes exert a role in neoplastic transformation and progression. As epigenetic mechanisms, converse to genetic mutations, are potentially reversible, they are an interesting and promising therapeutic target for the treatment of PanNETs.
We reviewed main epigenetic alterations associated with the development, biological and clinical features and progression of PanNETs, as well as emerging therapies targeting epigenetic changes, which may prove effective for the treatment of human PanNETs.
Constant advances in the PanNET medical approach, as reported in the clinical and therapeutic recommendations of ESMO, improved the overall survival of patients over the years. However, over 60% of the patients with metastatic disease still have poor prognosis. Epigenetic regulator drugs, currently approved to treat some human malignancies, that showed anti-tumoral activity also on PanNETs, in pre-clinical and clinical studies, could concur to ameliorate the prognosis and OS of advanced and metastatic PanNET, in combination with surgery and currently employed medical therapies.
高分化胰腺神经内分泌肿瘤（PanNETs）是内分泌胰腺原发性肿瘤的异质性群体。染色质重塑失调、基因表达改变、非编码区整体DNA低甲基化、DNA高甲基化以及肿瘤抑制基因启动子沉默是PanNETs中常见的表观遗传变化。这些变化在肿瘤转化和进展中发挥作用。由于与基因突变相反，表观遗传机制具有潜在的可逆性，因此它们是治疗PanNETs的一个有趣且有前景的治疗靶点。
我们综述了与PanNETs的发生、生物学和临床特征及进展相关的主要表观遗传改变，以及针对表观遗传变化的新兴疗法，这些疗法可能被证明对治疗人类PanNETs有效。
正如欧洲肿瘤内科学会（ESMO）的临床和治疗建议中所报道的，PanNET医学方法的不断进步多年来提高了患者的总生存率。然而，超过60%的转移性疾病患者预后仍然很差。在临床前和临床研究中显示对PanNETs也具有抗肿瘤活性的表观遗传调节药物，目前已被批准用于治疗某些人类恶性肿瘤，与手术和目前采用的医学疗法相结合，可能有助于改善晚期和转移性PanNET的预后和总生存期。
