Moody Terry W, Nuche-Berenguer Bernardo, Jensen Robert T
aDepartment of Health and Human Services, National Cancer Institute, Center for Cancer Research, Office of the Director bNational Institutes of Health, National Institute of Diabetes, Digestive and Kidney Disease, Digestive Diseases Branch, Bethesda, Maryland, USA.
Curr Opin Endocrinol Diabetes Obes. 2016 Feb;23(1):38-47. doi: 10.1097/MED.0000000000000218.
To summarize the roles of vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase activating polypeptide (PACAP) and their receptors (VPAC1, VPAC2, PAC1) in human tumors as well as their role in potential novel treatments.
Considerable progress has been made in understanding of the effects of VIP/PACAP on growth of various tumors as well as in the signaling cascades involved, especially in the role of transactivation of the epidermal growth factor family. The overexpression of VPAC1/2 and PAC1 on a number of common neoplasms (breast, lung, prostate, central nervous system and neuroblastoma) is receiving increased attention both as a means of tumor imaging the location and extent of these tumors, as well as for targeted directed treatment, by coupling cytotoxic agents to VIP/PACAP analogues.
VIP/PACAP has prominent growth effects on a number of common neoplasms, which frequently overexpressed the three subtypes of their receptors. The increased understanding of their signaling cascades, effect on tumor growth/differentiation and the use of the overexpression of these receptors for localization/targeted cytotoxic delivery are all suggesting possible novel tumor treatments.
总结血管活性肠肽(VIP)/垂体腺苷酸环化酶激活多肽(PACAP)及其受体(VPAC1、VPAC2、PAC1)在人类肿瘤中的作用以及它们在潜在新疗法中的作用。
在理解VIP/PACAP对各种肿瘤生长的影响以及所涉及的信号级联反应方面取得了相当大的进展,尤其是在表皮生长因子家族的反式激活作用方面。VPAC1/2和PAC1在多种常见肿瘤(乳腺癌、肺癌、前列腺癌、中枢神经系统肿瘤和神经母细胞瘤)中的过表达越来越受到关注,这既作为一种对这些肿瘤的位置和范围进行肿瘤成像的手段,也作为一种通过将细胞毒性药物与VIP/PACAP类似物偶联进行靶向治疗的方法。
VIP/PACAP对多种常见肿瘤具有显著的生长作用,这些肿瘤常常过度表达其三种受体亚型。对其信号级联反应、对肿瘤生长/分化的影响以及利用这些受体的过表达进行定位/靶向细胞毒性递送的认识不断增加,所有这些都提示了可能的新型肿瘤治疗方法。