Gastrointestinal and Endocrine Tumor Unit, Medical Oncology Department, Vall Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Pg Vall d'Hebron, 119-129 08035, Barcelona, Spain.
Curr Treat Options Oncol. 2021 Mar 30;22(5):43. doi: 10.1007/s11864-021-00834-3.
Neuroendocrine neoplasms (NENs) constitute a heterogenous group of malignancies. Translational research into NEN cell biology is the cornerstone for drug development strategies in this field. Somatostatin receptor type 2 (SSTR2) expression is the hallmark of well-differentiated neuroendocrine tumors (NETs). Somatostatin analogs and peptide receptor radionuclide therapy (PRRT) form the basis of anti-SSTR2 treatment onto new combination strategies, antibody-drug conjugates and bispecific antibodies. Classical pathways involved in NET development (PI3K-Akt-mTOR and antiangiogenics) are reviewed but new potential targets for NET treatment will be explored. Epigenetic drugs have shown clinical activity in monotherapy and preclinical combination strategies are more than attractive. Immunotherapy has shown opposite results in different NEN settings. Although the NOTCH pathway has been targeted with disappointing results, new strategies are being developed. Finally, after years of solid preclinical evidence on different genetically engineered oncolytic viruses, clinical trials for refractory NET patients are now ongoing.
神经内分泌肿瘤（NENs）是一组异质性的恶性肿瘤。NEN 细胞生物学的转化研究是该领域药物开发策略的基石。生长抑素受体 2（SSTR2）的表达是分化良好的神经内分泌肿瘤（NETs）的标志。生长抑素类似物和肽受体放射性核素治疗（PRRT）构成了抗 SSTR2 治疗的基础，在此基础上发展出了新的联合策略、抗体药物偶联物和双特异性抗体。本文回顾了涉及 NET 发展的经典途径（PI3K-Akt-mTOR 和抗血管生成），但也将探讨 NET 治疗的新潜在靶点。表观遗传学药物在单药治疗中已显示出临床活性，且临床前联合策略极具吸引力。免疫疗法在不同的 NEN 环境中产生了相反的结果。尽管 NOTCH 途径已被靶向，但新的策略正在开发中。最后，经过多年对不同基因工程溶瘤病毒的扎实的临床前研究，目前正在进行针对难治性 NET 患者的临床试验。
