Table 1.
Clinical trials targeting CAFs in PDAC.
| S. No. | Target | Name of Therapeutic | Rationale Based on Pre-Clinical Studies | Current Status | ClinicalTrials.gov Identifier |
|---|---|---|---|---|---|
| 1. | Hedgehog Pathway | IPI-926 | Inhibition of the Hedgehog Pathway, leading to reduced CAF activation |
Phase II was halted due to the early detection of a shorter median overall survival (OS) in the experimental arm, compared to the placebo arm. | NCT01130142 |
| 2. | Hedgehog Pathway | Vismodegib | The phase Ib/II randomized clinical trial, evaluating the addition of Vismodegib to gemcitabine, showed no treatment benefit for OS or progression free survival (PFS). |
NCT01195415 | |
| 3. | Hyaluronic acid | PEGPH20 | Depletion of stroma by PEGPH20, which may synergize with immunotherapy | Clinical trials failed to show any benefit. | NCT03634332 |
| 4. | Angiotensin receptor | Losartan | Attenuation of collagen and hyaluronan deposition by CAFs through inhibition of TGF-β signaling | Encouraging results in locally advanced PDAC | NCT03563248 |
| 5. | LOXL2 | Simtuzumab | Inhibition of matrix-remodeling enzyme Lysyl oxidase-like 2, an ECM remodeling enzyme | Study completed, and addition of Simtuzumab to gemcitabine did not improve clinical outcomes |
NCT01472198 |
| 6. | CXCL12-CXCR4 Axis | Olaptesed (NOX-A12) | Modulation of PDAC TME by reducing immunosuppressive factors, as CXCL12 secreted by iCAFs promotes tumorigenesis by reducing CD8 T cell infiltration | Clinical trial ongoing | NCT03168139 |
| 7. | CXCL12-CXCR4 Axis | BL-8040 CXCR4 Antagonist |
Clinical trial ongoing | NCT02826486 | |
| 8. | IL-6 | Siltuximab | Combination of IL-6 and PD-L1 blockade decreases tumor growth, improves survival, and leads to increased infiltration of effector CD8+ T cells | Clinical trial ongoing | NCT04191421 |
| 9. | Vitamin D receptor (VDR) | Paricalcitol (Vitamin D Receptor Agonist) | Modulating signaling in tumor microenvironment. CAFs highly express VDR, and treating them with Vitamin D can induce a quiescent phenotype |
Clinical trials ongoing | NCT03520790 |
| NCT03300921 | |||||
| NCT02754726 | |||||
| 10. | Vitamin D receptor (VDR) | Vitamin D3 | Clinical trials ongoing | NCT03472833 | |
| 11. | Stroma | All Trans Retinoic Acid (ATRA) | Inducing CAF quiescence and decreasing motility, leading to decreased tumor growth through decreased Wnt-β Catenin signaling | Clinical trials ongoing | NCT03307148 |
| 12. | IL-1R | Anakinra (IL-1R antagonist) |
By switching iCAF to a myCAF phenotype | Clinical trials ongoing | NCT02550327 |