Funding covers five cancer-research projects underway

More than $1 million in grants has been approved for five cancer research projects being conducted at The Hormel Institute, University of Minnesota-Mayo Clinic.
Three grants involve studies related to the prevention, diagnosis and treatment of prostate cancer. The others will perform research related to pancreatic cancer, which has a high mortality rate, and other cancers, including bladder cancer.
Funding periods vary for the grants, which total about $1.3 million overall, running through either 2011 or 2012.
Dr. Mohammad Saleem Bhat (molecular chemoprevention and therapeutics), Dr. PeiWen Fei (tumor suppressors and cancer susceptibility syndromes) and Dr. Junxuan Lu (cancer biology) – are the principal investigators who applied for and received these grants:

• $371,672 funded by the National Institutes of Health (through March 2012) – “An Oriental Herbal Cocktail for Prostate Cancer Chemoprevention.” The long-term goal for Dr. Junxuan Lu and his team is to develop an orally effective, non-toxic alternative and complementary medicine modality from Oriental herbs for prostate cancer chemoprevention.
In preliminary studies, his team has found that the ethanol extract of Ka-mi-kae-kyuk-tang (KMKKT) consisting of 10 Chinese and Korean herbs has strong anti-angiogenesis activity. That is, it helps inhibit the formation of blood vessels from cancerous tissue and provides anti-metastasis action. At the doses tested, KMKKT did not have adverse side effects. The grant-funded work will test the efficacy for cancer prevention in animal models and safety for long-term use.

• $316,438 funded by the National Institutes of Health (through May 2011) – “Roles of the Fanconi Anemia Pathway in Bladder Tumorigenesis.” People with the rare human genetic disease Fanconi anemia (FA) have a higher incidence of cancer. FA disease is caused by mutations in any one of 13 known genes that generate proteins functioning in the FA signaling pathway.
“Whether this pathway has a role in human cancers in individuals who do not have FA has not been clearly determined,” Dr. PeiWen Fei said.
As a long-term goal, Fei’s team wants to use FA as a unique genetic model system to dissect the FA protein signaling pathway, determine how FA proteins mediate tumor suppression and investigate the potential of targeting the FA pathway as a therapeutic approach in cancer treatment. It is the first study to analyze how a candidate oncogene interferes with the functionality of the FA pathway in human cancer, including bladder cancer. Fei described it as a “new and exciting concept in the field of cancer research.” Results from the project might lead to the development of more cancer-fighting methods.

• $252,405 funded by the U.S. Department of Defense (through July 2012) – “The Role of Polycomb Group Gene Bmi-1 in the Development of Prostate Cancer.” About one in 10 U.S. men develops prostate cancer in their lifetime. With this grant, Dr. Mohammad Saleem Bhat’s team is studying the Bmi-1 protein that plays a role in the proliferation of prostate cancer cells.
The hope is to use the Bmi-1 protein as a biomarker for the diagnosis and staging of prostate cancer, Bhat said. It hopefully will lead to future in-depth studies establishing Bmi-1 as a suitable target to monitor the therapeutic response in prostate cancer patients. Recently, Dr. Bhat’s section extended a collaboration with Mayo Clinic’s Department of Urology to investigate the mechanism through which Bmi-1 plays a role in the development of prostate cancer.

• $183,811 funded by the National Institutes of Health (through April 2011) – “Delaying the Hormone Refactory Prostate Cancer by Dietary Triterpene Lupeol.” Lupeol is a chemical constituent found in fruits and vegetables, such as olives, strawberries, grapes, apples, cucumbers and medicinal herbs.
This study looks at Lupeol treatment possibly inhibiting tumor growth in the prostate, Bhat said. Prostate cancer manifests into two forms – androgen dependent (which is treatable with anti-hormone therapy) and androgen independent (which is highly aggressive and seldom responds to anti-hormone therapy or chemotherapy).
This grant focuses on whether Lupeol could delay or prevent the development of androgen-independent prostate cancer. “Lupeol selectively targets cancer cells while sparing normal cells,” said Bhat, who emphasizes it also is a “non-toxic agent.”

• $165,000 funded by the American Institute for Cancer Research (through February 2012) – “Targeting of cFLIP by Lupeol, a Dietary Triterpene, for the Chemoprevention of Pancreatic Cancer.” Bhat’s team has discovered that the cFLIP protein contributes to the failure of chemotherapy in pancreatic-cancer patients. Notably, Lupeol was identified by Bhat’s team to possess the ability to lower the levels of the cFLIP protein and inhibit its activity in pancreatic-cancer cells.
“The treatment options for pancreatic cancer are limited and unsatisfactory,” Bhat said. “This proposal should be extremely valuable in providing a novel and diet-based agent for treatment and prevention of pancreatic cancer.”
In the future, the hope is for Lupeol to become available as a supplement for cancer prevention and be developed as a therapeutic agent for treating cancer, Bhat said.
Research by Bhat’s team shows that Lupeol, when combined with other chemotherapeutic agents – such as gemcitabine and cisplatin – enhances their ability to target and kill cancer cells. Bhat suggests that Lupeol also might lessen the side effects of chemotherapeutic agents, allowing patients to take lesser dosages of these agents.
“The ultimate aim of these projects is to take them to the translational level to be tested under clinical settings,” Bhat said.

The Hormel Institute is a world-renowned cancer research center, specializing in work leading to cancer prevention and control. It currently has 11 cancer research departments, with 130 employees.