Fibroblast activation protein (FAP)-放射性配基疗法可能对某些患者有效，但不能治愈。FAP-放射性配基可直接照射FAP+癌相关成纤维细胞，在某些癌症中可照射FAP+肿瘤细胞；此外，它们通过交叉火力和旁观效应间接照射肿瘤组织中的FAP-细胞。在这里，我们讨论了通过干扰DNA损伤修复、免疫疗法和共靶向癌相关成纤维细胞来改善FAP-放射性配基疗法的潜力。由于FAP-放射性配基对肿瘤及其微环境的分子和细胞影响尚未得到研究，我们呼吁未来的研究来填补这方面的知识空白，以便开发更有效的FAP-放射性配基疗法。版权所有©2023 Elsevier Inc.。保留所有权利。

Fibroblast activation protein (FAP)-radioligand therapy might be effective in some patients without being curative. FAP-radioligands deliver ionizing radiation directly to FAP+ cancer-associated fibroblasts and, in some cancers, to FAP+ tumor cells; in addition, they indirectly irradiate FAP- cells in tumor tissue via cross-fire and bystander effects. Here, we discuss the potential to improve FAP-radioligand therapy through interfering with DNA damage repair, immunotherapy, and co-targeting cancer-associated fibroblasts. As the molecular and cellular effects of FAP-radioligands on the tumor and its microenvironment have not been investigated yet, we call for future research to close this gap in knowledge, which prevents the development of more effective FAP-radioligand therapies.Copyright © 2023 Elsevier Inc. All rights reserved.