Table 2.

Extracellular mechanisms of thereapeutic resistance in pancreatic cancer

Potential therapeutic targets	Extracellular response	Ref.
K-ras mutant oncogene	Proliferation of desmoplastic reaction (leukocytes, fibroblasts, endothelial cells, neuronal cells, collagen, hyaluron): upregulation of GM-CSF	Chu et al[78]; Neesse et al[79]; Ying et al[81]; Nolan-Stevaux et al[82]; Bayne et al[87]
Sonic hedgehog (SHH)	Growth and differenatiation of stromal fibroblasts	Bailey et al[83]; Tian et al[84]; Olive et al[85]
Tumor associated macrophages (TAMs); cancer associated fibroblasts (CAFs); regulatory T-cells (Treg); myeloid derived suppressor cells	Evasion of the immune system	Bayne et al[87]; Pylayeva-Gupta et al[88]
Desmoplastic reaction	Anti-angiogenesis; hypoxic tumor environment	Komar et al[86]

K-ras: Kinase-rat sarcoma; GM-CSF: Granulocyte macrophage colon-stimulating factor.