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Table 1 PDAC stroma-associated therapeutic targets

From: The role of stromal cancer-associated fibroblasts in pancreatic cancer

Drug Target Mechanism Preclinical results Clinical results Author
All-trans retinoic acid + gemcitabine PDAC and stroma CAF deactivation to quiescence with vitamin A storage capacity Decrease in transcription factors in PDAC cells
Increased markers of stromal quiescence
Decrease in EMT
N/A Carapuca et al. [50]
SPARC overexpression + nab-paclitaxel PDAC via stroma Sequestration of drug by SPARC 2.8× gemcitabine concentration within tumor 50% reduction in PDAC cell proliferation
Increase in endothelial proliferation
Von Hoff et al. [12]
PEGPH20 + gemcitabine Stroma Stromal degradation by hyaluronidase Significant depletion of hyaluronan 4× increase microvessel lumen diameter
Increase in drug delivery to tumor within first 24 h
7.2-month progression-free survival (PFS) and 12-month OS in tumors highly expressing hyaluronan
Overall response rate of 25 and 67% in high HA tumors vs. 13% in standard therapy
Minimal side effects
Hingorani et al. [52]
Momelotinib, ruxulitinib + nab-paclitaxel or gemcitabine JAK2 JAK2 inhibition Depletion of stroma
Decreased PSC activation
Diminished and altered collagen structures
OS 0.79 and PFS 0.72 hazard ratio (HR) ruxolitinib vs. placebo
High inflammation subgroup: OS HR 0.47 vs. placebo
Ruxolitinib failed phase III, momelotinib ongoing
Hurwitz et al. [53]
Dawkins et al.
Koh et al.
Wormann et al. [33]
SHH inhibitors SHH Decreased stroma expansion Conflicting results Conflicting results Olive et al. [5]
Kim et al. [54]
Laheru et al.
Dejesus-Acosta et al.
Pasireotide CAFs Somatostatin analog Reduced tumor growth
Reduced chemoresistance
N/A Duluc et al. [47]