Pancreatic cancer stroma: Understanding biology leads to new therapeutic strategies

Table 1 Recent and ongoing preclinical and clinical studies of experimental therapies targeting tumor microenvironment of pancreatic ductal adenocarcinoma

Stromal component	Therapeutic target	Treatments in preclinical and clinical trials	Up to date preclinical/clinical trial results
PSCs/fibroblasts	FAP	Sibrotuzumab (colorectal cancer)	Hofheinz et al[99], 2003
ECM	Hyaluronan	PEGPH20	Strimpakos et al[91], 2013
	MMPs	BAY 12-9566	Moore et al[100], 2003
		Marimastat	Bramhall et al[101], 2002
Immune cells	PD-L1	BMS-936559	Brahmer et al[102], 2012
	CTLA-4	Ipilimumab	Le et al[95], 2013
	CD8+ T cells	GVAX	Lutz et al[93], 2011
			Laheru et al[94], 2008
	CD40	CP-870,893	Beatty et al[103], 2013
Signaling pathways mediating tumor-stroma interactions	Smo/SHh	Vismodegib (GDC-0449)	Stephenson et al[90], 2011
		IPI-926
	Type II TGFβ receptor	Trabedersen	Oettle et al[92], 2009
	γ-secretase (Notch pathway)	PF-03084014 (preclinical)	Yabuuchi et al[78], 2013
			(preclinical)
	HGF/c-met	Many different compounds (solid cancers)	Venepalli et al[104], 2013
			(solid cancers)
	Different molecules in NF-κB cascade	Many different compounds (i.e., curcumin, proteasome inhibitor)	Arlt et al[105], 2012

ECM: Extracellular matrix; MMP: Matrix metalloproteinase; PD-L1: Programmed death receptor ligand 1; CTLA-4: Cytotoxic T-lymphocyte antigen 4; SHh: Sonic hedgehog; Smo: Smoothened; TGFβ: Transforming growth factor β; HGF: Hepatocyte growth factor; NF-κB: Nuclear factor κ-B; PSC: Pancreatic stellate cell; FAP: Fibroblast activation protein.