Table 1.
Selected therapeutic stromal targets and clinical trials.
| Target | Candidate Drug and Combination Regimen |
Drug Type | Mechanism | Outcomes |
|---|---|---|---|---|
| LOXL2 | Simtuzumab plus gemcitabine | Blocking antibody | Destabilizes collagen networks | Negative outcome (phase II [58]) |
| Renin−angiotensin system | Losartan plus FOLFIRINOX followed by chemoradiotherapy (as neoadjuvant therapy) | Small molecule inhibitor | Reduces collagen and hyaluronan | Downstaging (phase II [59]) |
| Focal adhesion kinases | Defactinib plus pembrolizumab and gemcitabine | Small molecule inhibitor | Prevents integrin signaling | Clinical trials in phase I completed ([60], NCT02546531) |
| Hyaluronan | PEGPH20 plus nab-paclitaxel and gemcitabine | Enzyme | Degrades hyaluronan | Improved PFS (phase II [61]) |
| PEGPH20 plus modified FOLFIRINOX | Detrimental effects (phase Ib/II [62]) |
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| PEGPH20 plus nab-paclitaxel and gemcitabine | Negative outcome (phase III [63]) |
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| Hedgehog | Saridegib plus gemcitabine | Small molecule inhibitor | Prevents/reduces CAF activation | Worse clinical outcome (phase Ib/II, NCT01130142) |
| CXCR4-CXCL12 | Motixafortide plus pembrolizumab and chemotherapy | Small molecule inhibitor | Interferes with CAF signaling | Improved objective response rate (phase II [64,65]) |
| FAP | RO6874281 | Small molecule inhibitor | Interferes with CAF function | Clinical trials in phase I ongoing (NCT02627274) |