Cancer as a disease is one of the world's worst public health and financial problems. Statistics from the American Cancer Society for 2004 indicate that an estimated 1.4 million people were diagnosed with cancer in the U.S. and 564,000 people or about 1,500 people a day are expected to die of cancer this year in the U.S. alone. The National Institutes of Health estimate overall costs for cancer in 2005 at $209.9 billion: $74 billion for direct medical costs; $17.5 billion for indirect morbidity costs; and $118.4 billion for indirect mortality costs related to lost productivity due to premature death.

PANACEA'S CANCER PROGRAM

Human aspartyl (asparaginyl) ß-hydroxylase has been established as both an excellent biomarker and drug target for cancer diagnosis and therapy based on its biochemical and cellular properties and known biological function:

• HAAH over-expression was initially discovered in liver cancer, but has now been identified in more than 20 different types of cancer. HAAH is not detected to an appreciable extent in normal tissues including non-cancerous proliferative disorders.
• Over-expression of HAAH is sufficient to cause cancer. When HAAH over-expressing cells are injected into a mouse they form tumors.
• Loss of HAAH function is not detrimental to normal cellular function; requirement for its activity is restricted to embryonic cell development and tumor cell function.
• In tumor cells HAAH over-expression results in its relocalization from an internal cellular compartment to the cell surface where it is accessible to external treatments (e.g. antibodies).
• HAAH is an enzyme that hydroxylates EGF-like domains in specific proteins altering their function. The mislocalization of HAAH to the surface in tumor cells is thought to result in improper hydroxylation of these proteins many of which have been associated with alterations in cellular regulatory pathways leading to malignant disease (e.g. Notch).
• In tumor cells HAAH drives cellular proliferation, motility and invasiveness; properties that are crucial to disease progression.