TGFβ Signaling in the Pancreatic Tumor Microenvironment
Abstract
:Simple Summary
Abstract
1. Introduction
2. Canonical TGFβ Signaling in PDAC
3. Non-Canonical TGFβ Signaling in PDAC
4. TGFβ in Fibrosis and Stromal Cell Biology
5. TGFβ and the Immune Microenvironment
6. Clinical Trials Exploring TGFβ Signal Inhibition in PDAC
7. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
Pancreatic ductal adenocarcinoma | (PDAC) |
Transforming Growth Factor β | (TGFβ) |
Tumor microenvironment | (TME) |
Epithelial-to-mesenchymal transition | (EMT) |
Pancreatic stellate cells | (PSCs) |
Cancer-associated fibroblasts | (CAFs) |
Extracellular matrix | (ECM) |
MicroRNAs | (miRNAs) |
DNA mismatch repair | (dMMR) |
High microsatellite instability | (MSI-H) |
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TGFβ Inhibitor | Additional Therapy | Phase | Number of Patients | Prior Lines of Therapy | Response Rate | Median PFS | Median OS | Ref |
---|---|---|---|---|---|---|---|---|
Galunisertib | Durvalumab | Ib | 37 | ≤2 | 3.1% | 1.87 | 5.72 | [178] |
Galunisertib | - | II | 52 | ≥1 | 3.8% | 2.86 | 7.10 | [177] |
Galunisertib | Gemcitabine | II | 104 | ≥1 | 10.6% | 4.11 | 8.90 | [177] |
M7824 | Gemcitabine | II | 7 | ≥1 | NR | 1.40 | 3.50 | NCT 03451773 |
AP 12009 | - | Ib | 62 | - | NR | NR | NR | NCT 00844064 |
Galunisertib | Gemcitabine | Ib | 6 | - | NR | NR | NR | NCT 02154646 |
TGFβ Inhibitor | Additional Therapy | Phase | Enrolment Criteria | Prior Treatments | Clinical Trial Number |
---|---|---|---|---|---|
SHR-1701 | Gemcitabine /Nab-Paclitaxel | Ib/II | Advanced or Metastatic PDAC | - | NCT04624217 |
Vactosertib (TEW-7197) | FOLFOX | Ib | Metastatic PDAC | Gemcitbine /Nab-Paclitaxel | NCT03666832 |
Vactosertib (TEW-7197) | Nal-Irinotecan /5-FU | Ib | Metastatic PDAC | Gemcitabine /Nab-Paclitaxel | NCT04258072 |
M7824 | M9241/RT | I/II | Advanced or Metastatic PDAC | - | NCT04327986 |
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Principe, D.R.; Timbers, K.E.; Atia, L.G.; Koch, R.M.; Rana, A. TGFβ Signaling in the Pancreatic Tumor Microenvironment. Cancers 2021, 13, 5086. https://doi.org/10.3390/cancers13205086
Principe DR, Timbers KE, Atia LG, Koch RM, Rana A. TGFβ Signaling in the Pancreatic Tumor Microenvironment. Cancers. 2021; 13(20):5086. https://doi.org/10.3390/cancers13205086
Chicago/Turabian StylePrincipe, Daniel R., Kaytlin E. Timbers, Luke G. Atia, Regina M. Koch, and Ajay Rana. 2021. "TGFβ Signaling in the Pancreatic Tumor Microenvironment" Cancers 13, no. 20: 5086. https://doi.org/10.3390/cancers13205086