Mayo Researchers Make Progress In Fight Against Malignant Form Of Cancer
Correction: This article has been updated to clarify RedHill BioPharma's role and the specific actions of the drug.
Mayo Clinic researchers working on ways to battle a rare but highly malignant form of cancer reported making progress in the fight this month by testing an experimental drug that appears to inhibit a key enzyme within cancerous cells.
The encouraging results of Mayo’s participation in the non-clinical study of the drug Yeliva, developed initially in Pennsylvania and now licensed and under development by an Israeli company, add to the clinic’s long-standing reputation as a cancer research powerhouse and boosts hope for a long-sought effective treatment against bile duct cancer.
Known medically as cholangiocarcinoma, bile duct cancer is not common in the United States: According to the American Cancer Society, only about 2,000 to 3,000 Americans per year develop the disease. It is closely associated with irritation and inflammation of the bowels such as caused by parasitic infections, and thus is more prevalent in developing countries where these infections aren’t uncommon.
But the instances of bile duct cancer are increasing in Western countries as well. For instance, number of mortalities in Germany from intrahepatic cholangiocarcinoma tripled between 1998 and 2008, according to a 2011 study published in Scandinavian Journal of Gastroenterology. The reasons for that spike remain a mystery.
Meanwhile, the odds for those who contract this type of cancer are not good. The five-year survival rate for those with localized cases of intrahepatic cholangiocarcinoma is only 15 percent. This low survival rate hasn’t improved for 30 years, the cancer society reports.
Part of the reason is that there are some serious complicating factors. Although liver transplantation and other radical surgery can cure some patients, the fact is most bile duct cancer victims are only diagnosed at later stages when surgery is no longer an option. Also, conventional chemotherapy and radiotherapy generally aren’t effective against it.
Thus, there is an urgent need to develop new and effective therapeutics, and the results of a non-clinical study led by Mayo Clinic researchers using the experimental drug Yeliva, developed by Dr. Charles Smith of Harrisburg, Pa.-based Apogee Biotechnology have provided some hope of developing an inhibitor for various kinds of gastroenterological cancers, including cholangiocarcinoma.
The team from Mayo’s gastroenterology/hepatology department and the clinic’s Cancer Center published the results of a study they co-authored in the March issue of the medical journal Oncotarget. (The team included Drs. Xiwei Ding, Roongruedee Chaiteerakij, Catherine Moser, Hassan Shaleh, Jeffrey Boakye, Gang Chen, Albert Ndzengue, Ying Li, Yanling Zhou, Shengbing Huang, Frank Sinicrope and Lewis Roberts).
They found Yeliva was effective in blocking the action of the enzyme sphingosine kinase-2 (SK2) in cholangiocarcinoma cancer cells. The SK2 enzyme, associated with inflammation, is known to be a key factor in the spread of several different kinds of cancers.
The Mayo researchers, along with Dr. Smith and others, concluded that Yeliva’s targeting of SK2 in the affected cells inhibited cancer proliferation and induced apoptosis – or self-destruction – in the cholangiocarcinoma cells.
They also determined that Yeliva is effective in preventing the activation of a cancer-spreading “signaling pathway” protein in the cancer cells. Called the STAT3 pathway, there is strong evidence to suggest that aberrant STAT3 signaling promotes human cancers by inducing cancer cell proliferation.
Yeliva is being developed by RedHill Biopharma Ltd. (Nasdaq: RDHL) of Tel Aviv, Israel, which says it is currently in Phase II clinical trials (although not at Mayo). Its development has been funded primarily by grants and contracts from U.S. federal and state government agencies awarded to Apogee, including the National Cancer Institute and the U.S. departments of Health and Defense.
RedHill Senior Vice President Reza Fathi said in a press release the results of the Mayo co-authored study were “important” and “suggest that Yeliva could potentially be effective in treating cholangiocarcinoma cancer.” The company, he said, is conducting various clinical trials of the drug, including a Phase I/II study on patients with lymphoma, as well as upcoming Phase II studies for its use in fighting multiple myeloma and in providing protection from damage caused by radiation therapy for cancer treatment.
Fathi added the company is also planning “additional clinical programs … for oncology, inflammatory and gastrointestinal indications.”