Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma or a Metaphor for Heterogeneity: From Single-Cell Analysis to Whole-Body Imaging
Abstract
:1. Introduction
2. Overview of Cancer-Associated Fibroblasts (CAFs) in PDAC: Heterogeneity and Plasticity
2.1. TME and CAFs
2.2. CAFs and Cellular Origin Heterogeneity
2.3. CAFs Phenotypical Heterogeneity
2.3.1. myCAFs
2.3.2. iCAFs
2.3.3. apCAFs
2.3.4. Other CAF Subtypes
2.4. CAFs Functional Heterogeneity
2.4.1. The Tumor-Promoting Functions of CAFs
2.4.2. The Tumor-Restraining Functions of CAFS
2.5. CAFs Heterogenous Spatial Distribution
2.6. CAFs Temporal Heterogeneity
2.7. CAFs Heterogeneity and Prognosis
2.8. CAFs Plasticity
3. FAPI PET Imaging in Pancreatic Cancer
3.1. Introduction to FAP-Targeted Radiopharmaceuticals
3.2. Advantages of FAPI PET
3.3. Clinical Applications of FAPI PET in Pancreatic Cancer
3.3.1. FAP Expression and Its Correlation with FAPI PET Uptake in Pancreatic Cancer
3.3.2. Comparison of FAPI PET and FDG PET Diagnostic Performance in Pancreatic Cancer
3.3.3. Prognostic and Predictive Value of FAPI PET in Pancreatic Cancer
3.3.4. Impact of FAPI PET in Pancreatic Cancer Staging and Management
3.3.5. FAPI PET in the Discrimination of Suspicious Pancreatic Lesions
4. Challenges and Future Directions
4.1. FAP Expression and FAP-Targeted PET Imaging
4.2. Future Potential of FAPI PET in Pancreatic Cancer
4.3. Future Directions: FAP-Targeted Radioligand Therapy
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Author and Publication Year | Study Design and Total Patient Number | Main Conclusion |
---|---|---|
Röhrich et al., 2020 [21] | Retrospective, n = 19 |
|
Liermann et al., 2021 [139] | Retrospective, n = 7 |
|
Pang et al., 2021 [20] | Retrospective, n = 36 |
|
Zhang et al., 2022 [128] | Prospective, n = 33 |
|
Lang et al., 2022 [140] | Retrospective, n = 25 |
|
Ding et al., 2023 [125] | Retrospective, n = 37 |
|
Liu et al., 2023 [129] | Retrospective, n = 51 |
|
Novruzov et al., 2023 [130] | Prospective, n = 7 |
|
Zhu et al., 2023 [137] | Prospective, n = 47 |
|
Rasinski et al., 2023 [141] | Prospective, n = 30 |
|
Ding et al., 2023 [132] | Prospective, n = 49 |
|
Lyu et al., 2023 [131] | Prospective, n = 31 |
|
Kessler et al., 2023 [126] | Prospective, n = 62 |
|
Spektor et al., 2024 [127] | Retrospective, n = 98 |
|
Li et al., 2024 [133] | Prospective, n = 62 |
|
Study ID | Study Design | Eligibility Criteria | Intervention | Primary Endpoint |
---|---|---|---|---|
Diagnostic clinical trials | ||||
NCT05083247 FAPI-PANC | Prospective sub-study, NR n= 30 | BR PDAC | Ga68-FAPI PET/CT | Establish a correlation between Ga68-FAPI PET/CT and histopathological and molecular biomarkers |
NCT05262855 | Phase 2, NR n = 60 | Resectable or BR PDAC | Ga68-FAPI PET/CT | Sensitivity, specificity, and accuracy to detect FAP-expressing cells using histopathology as true standard |
NCT05275985 | Prospective, NR n = 80 | Patients with pancreatic lesions | Ga68-FAPI PET/CT | SUV, number of patients who changed treatment, number of lesions detected, PFS, OS |
NCT05957250 PANSCAN-1 | Prospective study, NR n = 60 | Resectable or BR PDAC | Ga68-FAPI PET/CT | Sensitivity, specificity, and accuracy to detect FAP-expressing cells using histopathology as true standard |
NCT05518903 | Phase 2, NR n = 130 | Resectable or BR PDAC | Ga68-FAPI PET/CT | Sensitivity, specificity, and accuracy to detect FAP-expressing cells using histopathology as true standard |
FAP-targeted Radioligand Therapy Clinical Trials | ||||
NCT04849247 | Phase 1, NR n = 30 | Advanced or metastatic solid tumors | Ga68-DOTA-FAPI 177Lu-DOTA-FAPI | DLT RP2D |
NCT05432193 FRONTIER | Phase 1, NR n = 30 | Advanced or metastatic solid tumors (PDAC, CCA, EC CRC, Melanoma, HNSCC, sarcoma) | Ga68-PNT6555 177Lu-PNT6555 | Treatment-emergent AE |
NCT05723640 | Phase 1, NR | FAP+ advanced or metastatic solid tumors | 177Lu-LNC1004 | AE DLT |
NCT04939610 TablLuMIERE | Phase 1/2, NR n = 222 | FAP+ PDAC, BC, NSCLC | 177Lu FAP 2286 monotherapy and combination with chemotherapy | RP2D |
NCT06081322 | Phase 1, NR n = 29 | Advanced PDAC and CCA | 177Lu-EB-FAPI | AE Objective response rate |
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Saúde-Conde, R.; Arçay Öztürk, A.; Stosic, K.; Azurmendi Senar, O.; Navez, J.; Bouchart, C.; Arsenijevic, T.; Flamen, P.; Van Laethem, J.-L. Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma or a Metaphor for Heterogeneity: From Single-Cell Analysis to Whole-Body Imaging. Biomedicines 2024, 12, 591. https://doi.org/10.3390/biomedicines12030591
Saúde-Conde R, Arçay Öztürk A, Stosic K, Azurmendi Senar O, Navez J, Bouchart C, Arsenijevic T, Flamen P, Van Laethem J-L. Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma or a Metaphor for Heterogeneity: From Single-Cell Analysis to Whole-Body Imaging. Biomedicines. 2024; 12(3):591. https://doi.org/10.3390/biomedicines12030591
Chicago/Turabian StyleSaúde-Conde, Rita, Ayça Arçay Öztürk, Kosta Stosic, Oier Azurmendi Senar, Julie Navez, Christelle Bouchart, Tatjana Arsenijevic, Patrick Flamen, and Jean-Luc Van Laethem. 2024. "Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma or a Metaphor for Heterogeneity: From Single-Cell Analysis to Whole-Body Imaging" Biomedicines 12, no. 3: 591. https://doi.org/10.3390/biomedicines12030591
APA StyleSaúde-Conde, R., Arçay Öztürk, A., Stosic, K., Azurmendi Senar, O., Navez, J., Bouchart, C., Arsenijevic, T., Flamen, P., & Van Laethem, J.-L. (2024). Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma or a Metaphor for Heterogeneity: From Single-Cell Analysis to Whole-Body Imaging. Biomedicines, 12(3), 591. https://doi.org/10.3390/biomedicines12030591