Pancreatic cancer is an aggressive
malignancy with poor prognosis. Pancreatic
adenocarcinoma is one of the leading causes of
cancer-related deaths in the United States. Due to the aggressive nature of this
malignancy, there is a serious concern for identifying effective targets, and adopting novel strategies for
therapy. Members of the Specificity
Protein (Sp) family of
transcription factors, Sp1, Sp3, and Sp4 regulate the expression of a number of genes associated with
cancer cell proliferation, differentiation, and
metastasis. Sp1 levels are upregulated in
pancreatic cancer cell lines, and surgically resected human pancreatic
adenocarcinoma. Sp1 overexpression in
tumor tissues is associated with aggressive disease, poor prognosis and inversely correlated with survival. Sp1 is also known to affect angiogenesis by regulating the expression of
vascular endothelial growth factor and its receptors. Results from clinical studies suggest Sp1 as new
biomarker to identify aggressive pancreatic ductal
adenocarcinoma. The pharmacological inhibition of Sp1 using agents such as
celecoxib,
mithramycin,
curcumin, and
tolfenamic acid has showed promising results in pre-clinical studies and demonstrated
Sp transcription factors as potential targets for
pancreatic cancer therapy. This review summarizes studies showing the association of Sp
proteins with this
malignancy, with a special emphasis on pre-clinical studies that tested strategies to target
Sp transcription factors for inhibiting human
pancreatic cancer cell proliferation and
tumor growth in laboratory animals. The results showed remarkable efficacy and suggest that such approaches have the potential for high success in developing clinically relevant strategies for treating
pancreatic cancer.