Vitamin K boosts sorafenib (Nexavar) activity against pancreas, liver cancers

Sorafenib dosage requirement more than 50% less when combined with vitamin K.

Sorafenib or Nexavar and Vitamin K combination can work wonders against cancer of the pancreas and cancer of the liver- two of the most difficult forms of cancer- suggests studies.

Sorafenib (Nexavar) alongwith either of Vitamin K1 or vitamin K2 have shown activity against the growth of human cancer cells on both human pancreas cancer and hepatocellular carcinoma.

Sorafenib achieves this by inhibiting the extracellular signal-regulated kinase (ERK) pathway according to Brian Carr, M.D., Ph.D., a professor of Medical Oncology at the Jefferson Medical College of Thomas Jefferson University. ERK plays a major role in cell growth of cancers.

Sorafenib + Vitamin K was also tested sorafenib in pancreas cancer study. Each K vitamin in combination with sorafenib inhibited cell growth, induced cell death and decreased the expression of ERK. When combining vitamin K and sorafenib, the sorafenib dose required for inhibiting cancer cell growth decreased by more than 50 percent. This dose was ineffective when used alone, researchers have found.

“One of the attractions of the combination of sorafenib and vitamin K is that both of these agents are already approved for human use. K vitamins also have no known adult human toxicities, and appear to enhance the effects of sorafenib, thus requiring lower, less-toxic doses.”

There are few agents that have proven activity against pancreas cancer.

Vitamin K1 also enhanced the effects of sorafenib in liver cancer. Sorafenib is FDA-approved for the treatment of HCC, which typically arises on a cirrhotic liver, which tolerates conventional chemotherapy poorly.

However, vitamin K alone is a weak inhibitor of liver cancer growth. But its  combination inhibits the liver cancer growth, induces cell death and decreases the expression of ERK.

Nexavar is a multikinase inhibitor targeting several serine/threonine and receptor tyrosine kinases, is the tosylate salt of sorafenib.Sorafenib tosylate has the chemical name 4-(4-{3-[4-Chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)-N 2-methylpyridine-2-carboxamide 4-methylbenzenesulfonate.

Liver & Pancreatic cancers

Liver cancer (hepatocellular carcinoma) is a cancer arising from the liver. Liver cells (hepatocytes) make up 80% of the liver tissue. Thus, the majority of primary liver cancers (over 90 to 95%) arises from liver cells and is called hepatocellular cancer or carcinoma.

Liver cancer is the fifth most common cancer in the world. A deadly cancer, liver cancer will kill almost all patients who have it within a year. In 1990, the World Health Organization estimated that there were about 430,000 new cases of liver cancer worldwide, and a similar number of patients died as a result of this disease. About three quarters of the cases of liver cancer are found in Southeast Asia (China, Hong Kong, Taiwan, Korea, and Japan). Liver cancer is also very common in sub-Saharan Africa (Mozambique and South Africa).

The frequency of liver cancer in Southeast Asia and sub-Saharan Africa is greater than 20 cases per 100,000 population. In contrast, the frequency of liver cancer in North America and Western Europe is much lower, less than five per 100,000 population.

Pancreatic cancer occurs when cells in your pancreas develop genetic mutations. These mutations cause the cells to grow uncontrollably and to continue living after normal cells would die. These accumulating cells can form a tumor.

Types of pancreatic cancer include: Cancer that forms in the pancreas ducts (adenocarcinoma). Cells that line the ducts of the pancreas help produce digestive juices. The majority of pancreatic cancers are adenocarcinomas. Sometimes these cancers are called exocrine tumors and cancer that forms in the hormone-producing cells. Cancer that forms in the hormone-producing cells of the pancreas is called endocrine cancer. Endocrine cancers of the pancreas are very rare.

About 37,680 individuals are diagnosed with this condition and 34,290 die from the disease each year,each year in the United States alone. In Europe more than 60,000 are diagnosed every year. The prognosis is generally regarded as poor. Less than 5 percent of those diagnosed are still alive five years after diagnosis. Complete remission is still extremely rare.

Pancreatic cancer has one of the highest fatality rates of all cancers. Although it accounts for only 2.5% of new cases, pancreatic cancer is responsible for 6% of cancer deaths each year.