Copyright ©The Author(s) 2021.
World J Gastroenterol. May 14, 2021; 27(18): 2105-2121
Published online May 14, 2021. doi: 10.3748/wjg.v27.i18.2105
Table 1 Summary of stromal-targeting clinical trials in pancreatic cancer
DrugMechanism of actionBackbone therapyOutcome
Targeting stroma-promoting pathways in PDAC cells
Saridegib (IPI-926)SHH pathway inhibitorGemcitabine; mFOLFIRINOXNo improvement in OS or PFS (NCT01130142); No improvement in OS or PFS (NCT01383538)
VismodegibSHH pathway inhibitorGemcitabine; Gemcitabine + nab-paclitaxelNo improvement in OS or PFS (NCT01064622); No improvement in OS or PFS (NCT01088815)
SonidegibSHH pathway inhibitor (SMO receptor antagonist)Gemcitabine; Gemcitabine + nab-PaclitaxelNo improvement in OS or PFS (NCT01487785); No improvement in OS or PFS (NCT02358161)
GalunisertibTGF-β receptor inhibitorGemcitabine; Gemcitabine + DurvalumabOngoing trial (NCT01373164); Ongoing trial (NCT02734160)
LosartanTGF-β ligand inhibitorFOLFRINOX; Nivolumab + FOLFRINOXOngoing trial (NCT01821729); Ongoing trial (NCT03563248)
DefactinibFocal Adhesion Kinase inhibitorGemcitabine + PembrolizumabOngoing trial (NCT02546531)
AnakinraIL-1 receptor inhibitorGnP + CisplatinOngoing trial (NCT02550327)
Targeting stroma-promoting pathways in CAFs
PamrevlumabAntibody against CTGFGemcitabine + nab-paclitaxelOngoing trial (NCT03941093)
ParicalcitolVitamin D agonist; Inactivation of PSCGnP + Cisplatin; GnP + Hydroxychloroquine; 5FU/Leucovorin/liposomal Irinotecan; Pembrolizumab (2nd line)Ongoing trial (NCT04054362); Ongoing trial (NCT04524702); Ongoing trial (NCT03883919); Ongoing trial (NCT03331562)
ATRAInactivation of PSCGemcitabine + nab-paclitaxelOngoing trial (NCT03307148)
Targeting ECM
PEGPH20Hyaluronan degradationGemcitabine + nab-paclitaxel; mFOLFIRINOXNo improvement in OS or PFS (NCT02715804); Poor OS due to poor tolerance (NCT01959139)
SimtuzumabAntibody against LOXL2GemcitabineNo improvement in OS (NCT01472198)
CilengitideIntegrin inhibitorGemcitabineNo improvement in OS (ISRCTN13413322)
MarimastatMMP inhibitorGemcitabineNo improvement in OS
Bay-12-9566MMP inhibitorGemcitabineNo improvement in OS
HalofunginonePSC/CAF and SMAD2,3 inhibitor-Positive pre-clinical outcomes
PirfenidoneCell cycle inhibitor of CAF-Positive pre-clinical outcomes