The first disease model used in development of our technology is bile duct cancer. Bile is produced in the liver and carried via the bile ducts to the intestine, and has an important function in the digestion of fat. The bile ducts can be compared to a river. They start out as tiny channels (‘brooks’) inside the liver that empty into bigger channels (‘streams’) until they join the common bile duct that flows into the duodenum. The small bile ducts are located inside the liver (intrahepatic), while the larger bile ducts are found outside the liver (extrahepatic). Before entering the intestine (duodenum) the pancreatic duct joins the main duct. Clinically this explain why there sometimes is difficult to establish whether the cancer originate in the bile duct (bile duct cancer) or the pancreatic duct (pancreatic cancer).
Bile duct cancer
Bile duct cancer, or cholangiocarcinoma, is a tumour that forms in the biliary tree.
It is a rare and especially aggressive form of cancer that causes few symptoms in its early stages, and therefore is often quite advanced when it is diagnosed. This gives bile duct cancer a high mortality rate. If the cancer is diagnosed early and the tumour can be surgically removed either by local restriction or liver transplant, but more than 50 per cent of the operated patient relapse in short time after the procedure.
Bile duct cancer accounts for three per cent of all cancer of the digestive system, and is classified as an orphan disease. This form of cancer affects 1–2 in 100,000 persons in the USA and Europa, and is significantly more common in Asia.
For unknown reasons, the incidence is increasing. Due to failure in reports of the disease the patient group is considered twice the size. This is an aggressive disease both in Norway and in the rest of the world, and it is among the deadliest of all forms of cancer.
Major, unmet medical need
Surgery is usually not an option for patients who are diagnosed with bile duct cancer, as the cancer tends to be discovered at an advanced stage. The standard treatment today is chemotherapy with a combination of drugs, either Gemzitabin and Cisplatin or Gemzitabin and Capecitabin. The estimated life expectancy following diagnosis and standard treatment is only eleven months. The five-year survival rate for patients who are ineligible for surgery is 0-5%.
The diagnosis brings a marked reduction of quality of life, chemotherapy side effects, biliary drainage surgery and frequent hospital admissions.
The estimated global market for pharmacological treatment is USD 2,1–4,2 billion. The wide range of the estimate reflects uncertainties associated with reporting of cases.
As for today, standard treatment worldwide is a combination of generic (“off patent”) chemotherapy, whith expected survival of 11.5 months. A small group of patients have a FGFR2 mutation that might be suitable for targeted therapy. However, the accuracy of targeted therapy often falls behind expectations, leaving as much 80-85% of the treated patient without benefit of the drug. That said, for the responding patient the drug might be very beneficial. Overall the patient group have a large unmet need for better treatment options.