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Fibroblast activation protein-targeted radioligand therapy in various types of cancer: Background, clinical studies, and future development

Yizhen Pang1,2† ,  Liang Zhao1,2† ,  Jianhao Chen2 ,  Weizhi Xu3 ,  Jiayu Cai3 ,  Haojun Chen1,3* ,  Qin Lin1,2*
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1 The School of Clinical Medicine, Fujian Medical University, Fuzhou, China
2 Department of Radiation Oncology, Xiamen Cancer Center, Xiamen Key Laboratory of Radiation Oncology, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
3 Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Development and Translation of Radiopharmaceuticals, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
ARNM 2023, 1(2), 1667 https://doi.org/10.36922/arnm.1667
Submitted: 23 August 2023 | Accepted: 19 September 2023 | Published: 24 October 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Cancer is the leading cause of mortality worldwide. The proliferation and viability of cancer cells are intricately related to the complex tumor microenvironment in which they reside. Cancer-associated fibroblasts (CAFs) play a pivotal role in multiple stages of tumorigenesis, including tumor growth, invasion, metastasis, and resistance to treatment, through intricate crosstalk with tumor and immune cells. Targeted radionuclide therapy involves the systemic administration of small molecule drugs labeled with β-emitting or α-emitting radioisotopes, allowing precise targeting of tumor sites and delivering radiation directly to the tumor. Prostate-specific membrane antigen-targeted radioligand therapy (RLT) and somatostatin receptor-targeted peptide receptor radionuclide therapy (PRRT) have demonstrated favorable safety profiles and significant antitumor efficacy, leading to their approval by the Food and Drug Administration. Recently, the utilization of theranostic approaches that target overexpressed fibroblast activation proteins (FAPs) within the CAFs of the tumor stroma has demonstrated encouraging preliminary outcomes. This review aims to provide a concise summary of current clinical research outcomes and the applications of RLT based on FAP inhibitors in the context of solid tumors.

Keywords
Fibroblast activation proteins
Radioligand therapy
Immunotherapy
Synergistic effect
Funding
National Natural Science Foundation of China
Fujian Research and Training Grants for Young and Middle-aged Leaders in Healthcare, Key Scientific Research Program for Yong Scholars in Fujian
Fujian Natural Science Foundation for Distinguished Yong Scholars
Natural Science Foundation of Fujian Province
Key Medical and Health Projects in Xiamen
Xiamen Key Laboratory of Radiopharmaceuticals, Xiamen Key Laboratory of Radiation Oncology, Xiamen Clinical Research Center for Head and Neck Cancer, and 2021 National Clinical Key Specialty
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Conflict of interest
The authors declare that they have no conflicts of interest.
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