Steven Bernstein, M.D.

Co-director of the Lymphoma Biology Program at the James P. Wilmont Cancer Center, University of Rochester Medical Center in Rochester, New York

In June, the Lymphoma Research Foundation awarded two three-year grants to Steven Bernstein, M.D., for separate studies he is doing of new therapies for mantle cell lymphoma and follicular lymphoma, two rare and incurable diseases.  The mantle cell lymphoma preclinical study is focusing on a synthesized plant-derivative that is part of a family of naturally occurring compounds called triterpenoids, which have been shown to have anti-inflammatory and anti-carcinogenic activity.

"Dr. Michael Sporn, a cancer researcher at Dartmouth Medical School, created a series of synthetic triterpenoids and they initially showed that they had a relatively potent ability both in some settings as chemopreventative agents and in other settings as anti-tumor agents," says Dr. Bernstein.  "We were interested in this compound and decided to look at it in lymphoma."

Triterpenoids are compounds that affect the level of oxidation and energy a cell produces, and can be found in such spices as curcumin, or turmeric, and in herbal compounds called parthenolides.  The combination of these compounds may be able to affect cell mitochondria (the cells' energy source), inducing death in lymphoma cells.

"Some of our preliminary laboratory work with these agents show that they had quite potent effects inducing cell death of various types of lymphoma cell lines, including diffuse large cell lymphoma as well as mantle cell lymphoma," says Dr. Bernstein.  "Now, we are starting to look at not only their affect on mitochondria, but how they may affect other levels of cell oxidative stress or free radicals."

Understanding that effect, sayd Dr. Bernstein, may lead to use of triterpenoids and parthenolides to boost the effectiveness of chemotherapy drugs - especially targeted chemotherapy drugs - to kill lymphoma cells.

"We found that combining these agents with Velcade (bortezomib) seemed to augment the effect of the drug on the oxidative state of the cancer cell, so we are looking at how we can modulate that effect and use it to a therapeutic advantage in mantle cell lymphoma," says Dr. Bernstein.

Since it appears that triterpenoids may affect cells differently - by either protecting them from turning carcinogenic or by controlling cell growth - Dr. Bernstein's laboratory will test triterpenoids at different doses with a variety of targeted chemotherapy drugs to determine their safety and effectiveness.

Hope for New Therapy

Because triterpenoids as single agents are already being tested in clinical trials, according to Dr. Bernstein, it should not be long before the compounds will be ready for testing in combination with targeted chemotherapy agents in phase I trials of mantle cell lymphoma patients.

"I think over the next two years we will optimize what combinations make rational sense based on our understanding of their mechanism of action.  My hope is that we can then take all that we have learned in the laboratory and choose an optimal combination of triterpenoids to study in mantle cell lymphoma patients," says Dr. Bernstein.

By Jo Cavallo