VEGF and Angiogenesis in Pancreatic Cancer

Vascular endothelial growth factor (VEGF) plays a key role in the growth and metastasis of many tumors including pancreatic cancer.¹

Exocrine pancreatic cancers often have a poor patient outlook, as very few of these cancers are detectable at early stages. Patients usually experience no detectable symptoms until the cancer has spread to other organs. American Cancer Society estimates indicate only 10% of cancers of the pancreas to be contained within the pancreas at the time of diagnosis. Furthermore, only about half of these turn out to be truly resectable in a surgical procedure.² The 5-year relative survival rates of advanced stage exocrine pancreatic cancer (stage III or stage IV) is only 2% or less.² Even among those diagnosed with a local disease, the 5-year survival rate is only 23%.³ American Cancer Society (ACS) estimates 44,030 new cases of pancreatic cancer to occur in the United States in 2011, of which men comprise 22,050 cases and women 21,980 cases.

The rates of pancreatic cancer incidence have been growing since 1998 by 0.8% and 1.0% per year in men and women, respectively. Parallel to this increased incidence, death rates from pancreatic cancer were also reported to increase by 0.7% per year in men and by 0.1% per year in women between the years 2003 to 2007.³ ACS estimates 37,660 deaths to occur from pancreatic cancer in the year 2011, of which men comprise 19,360 cases and women 18,300 cases. The nearly identical incidence and mortality rates in pancreatic cancer are reflective of the ability of the disease to spread early and the inadequacy of current therapies.¹

Vascular endothelial growth factor (VEGF) plays an important role in the growth and metastasis of many tumors, including pancreatic cancer.¹ Several studies have found the expression of VEGF and its receptors, flt-1 (VEGFR-1) and KDR (VEGFR-2), in pancreatic cancer.^1,4,5 VEGF is also known to stimulate the growth of certain pancreatic cells in vitro, in a dose-dependent manner.^5,6 The role of the VEGF pathway in pancreatic tumor progression has also been studied in experiments involving animal models. In these studies, inhibitors of the VEGF tyrosine kinase, as well as anti-VEGF and anti-KDR antibodies, reduced the growth and angiogenesis of pancreatic tumors and enhanced the cytotoxic effect of certain therapeutic agents.^1,7-9 Furthermore, high VEGF levels in the serum correlate with advanced-stage postoperative disease recurrence and decreased survival in patients with pancreatic cancer.^1,10 High levels of VEGF expression in tumors have also been associated with a worse prognosis in this disease.^5,11

What has been learned from research during the past decade into the molecular biology of angiogenesis in pancreatic cancers may be summarized by the following key observations^1,4-6,10-12:

• Both VEGF and its receptors are overexpressed in pancreatic cancer
• VEGF acts as a strong mitogen for vascular endothelial cells in
  pancreatic cancer
• VEGF can participate in tumor spread and metastasis
• High levels of VEGF are correlated with disease progression and
  poor prognosis

For more information on a specific topic regarding VEGF and angiogenesis in pancreatic cancer, click on the links below.

References:

1.

Kindler HL, Friberg G, Singh DA, et al. J Clin Oncol. 2005;23:8033-8040. PMID: 16258101

2.

American Cancer Society. Pancreatic cancer. 2011. http://www.cancer.org/acs/groups/cid/documents/webcontent/003131-pdf.pdf. Accessed July 19, 2011.

3.

American Cancer Society. Cancer facts & figures 2011. http://www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/
cancer-facts-figures-2011. Accessed July 13, 2011.

4.

Itakura J, Ishiwata T, Friess H, et al. Clin Cancer Res. 1997;3:1309-1316. PMID: 9815813

5.

Itakura J, Ishiwata T, Shen B, et al. Int J Cancer. 2000;85:27-34. PMID: 10585578

6.

Büchler P, Reber HA, Büchler MW, et al. Ann Surg. 2002;236:738-749. PMID: 12454512

7.

Baker CH, Solorzano CC, Fidler IJ. Cancer Res. 2002;62:1996-2003. PMID: 11929816

8.

Bockhorn M, Tsuzuki Y, Xu L, et al. Clin Cancer Res. 2003;9:4221-4226. PMID: 14519649

9.

Bruns CJ, Shrader M, Harbison MT, et al. Int J Cancer. 2002;102:101-108. PMID: 12385004

10.

Karayiannakis AJ, Bolanaki H, Syrigos KN, et al. Cancer Lett. 2003;194:
119-124. PMID: 12706865

11.

Ikeda N, Adachi M, Taki T, et al. Br J Cancer. 1999;79:1553-1563. PMID: 10188906

12.

Niedergethmann M, Hildenbrand R, Wostbrock B, et al. Pancreas. 2002;
25:122-129. PMID: 12142733