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Circadian is developing a variety of drugs to block the interaction between VEGF Receptor-3 (VEGFR-3) and its ligands VEGF-C and VEGF-D. Drugs blocking this pathway would represent a novel and potentially revolutionary treatment approach for cancer patients. VEGFR-3 inhibitors may treat cancer by two mechanisms: First, inhibition of the ligands VEGF-C and VEGF-D blocks tumour angiogenesis, suppressing blood vessel development, starving tumours of oxygen and nutrients needed to grow. Second, tumours are known to metastasize through the lymphatic system. Tumour metastasis is often the direct factor leading to patient mortality. Blocking VEGFR-3 activation stops lymphangiogenesis, which in turn reduces the ability of tumours to spread. This approach to cancer treatment is potentially more effective than chemotherapy and may have greatly reduced side-effects. Circadian holds an extensive intellectual property position protecting its rights as the exclusive developer of this class of drugs.
Vascular Endothelial Growth Factor Receptor 3 (VEGFR-3) was originally reported in 1995 by Circadians collaborators in the Laboratory of Prof. Kari Alitalo at the University of Helsinki. It is also known as FLT-4. The University of Helsinki has assigned all of its extensive intellectual property rights related to VEGFR-3 to Circadian (under Circadians subsidiary, Vegenics Pty Ltd). Extensive characterization in the scientific literature has strongly validated VEGFR-3 as a promising new target for cancer therapy based upon its role in tumour angiogenesis and lymphangiogenesis. VEGFR-3 is increased in expression in blood vessels and lymphatic vessels surrounding tumours. During development, VEGFR-3 is critically required for the formation of the lymphatic system. Spread of cancer cells through the lymph is known as one of the key mechanisms of tumour metastasis. It is thought that blocking activation of VEGFR-3 will inhibit tumour growth by stifling blood supply and reduce the propensity for tumour spread by blocking metastasis through the lymph.
Vascular Endothelial Growth Factor C (VEGF-C) was first described in 1996 by Circadians collaborators in the Laboratory of Prof. Kari Alitalo. VEGF-C activates VEGFR-3 (as well as the related receptor VEGFR-2) thereby stimulating development of blood and lymphatic vessels. VEGF-C is known to be secreted by a variety of tumours. A number of publications has reported that increased expression of VEGF-C correlates with greater tumour aggression and a poorer prognosis. For example, Arinaga et al reported that non-small cell lung carcinoma patients whose tumours expressed VEGF-C had a poor survival expectancy. VEGF-C has also been shown to correlate with cancer progression in colorectal cancer. (Hu et al).
Vascular Endothelial Growth Factor D (VEGF-D) was first reported in 1998 by Circadians collaborators in the laboratory of Profs. Steve Stacker and Marc Achen at the Ludwig Institute for Cancer Research. As is the case for VEGF-C, it is known to be expressed by human tumour cells, and its expression is correlated with poor prognosis for cancer patients. In addition, VEGF-D expression has been strongly correlated with a serious lung disorder known as lymphangioleiomyomatosis (LAM). Circadian is investigating the development of a VEGF-D-based diagnostic test, as well as possible therapeutics for LAM based upon VEGF-D inhibition.