Surgical Specialties, Biochemistry and Immunology, University of Malaga, Spain.
Research and Innovation Unit, Hospital Costa del Sol, 29602 Marbella, Spain.
Curr Med Chem. 2024;31(39):6487-6509. doi: 10.2174/0109298673261625230924114406.
Different studies have highlighted the role of Substance P / Neurokinin 1 Receptor (SP/NK-1R) axis in multiple hallmarks of cancer including cell transformation, proliferation, and migration as well as angiogenesis and metastasis of a wide range of solid tumors including colorectal cancer. Until now, the selective high-affinity antagonist of human SP/NK1-R aprepitant (Emend) has been authorized by the Food and Drug Administration as a low dosage medication to manage and treat chemotherapy-induced nausea. However, increasing evidence in recent years support the potential utility of high doses of aprepitant as an antitumor agent and thus, opening the possibility to the pharmacological repositioning of SP/NK1-R antagonists as an adjuvant therapy to conventional cancer treatments. In this review, we summarize current knowledge on the molecular basis of colorectal cancer as well as the pathophysiological importance of SP/NK1-R and the potential utility of SP/NK-1R axis as a therapeutic target in this malignancy.
不同的研究强调了 P 物质/神经激肽 1 受体（SP/NK-1R）轴在多种癌症特征中的作用，包括细胞转化、增殖和迁移，以及多种实体瘤的血管生成和转移，包括结直肠癌。到目前为止，人类 SP/NK1-R 的选择性高亲和力拮抗剂阿瑞匹坦（Emend）已被食品和药物管理局授权为低剂量药物，用于管理和治疗化疗引起的恶心。然而，近年来越来越多的证据支持高剂量阿瑞匹坦作为抗肿瘤药物的潜在效用，从而为 SP/NK1-R 拮抗剂作为常规癌症治疗的辅助治疗的药理学重新定位开辟了可能性。在这篇综述中，我们总结了结直肠癌的分子基础以及 SP/NK1-R 的病理生理学重要性的最新知识，以及 SP/NK-1R 轴作为这种恶性肿瘤治疗靶点的潜在效用。
