Scientists’ Team Spirit Brings Discoveries to Patients Today and Tomorrow
Two years ago the James P. Wilmot Cancer Center got its biggest shot in the arm in years, in the form of an $11.5 million SPORE grant.
It was an exciting time at the Wilmot Cancer Center. A new building had just opened its doors to patients, and then the National Cancer Institute added Wilmot to its ambitious SPORE program, which is reserved for top-tier researchers and medical centers.
The award came with very high expectations about the pace of research and Wilmot’s ability to take advantage of collaborations with University of Arizona Cancer Center and the Massey Cancer Center at Virginia Commonwealth University to spawn new discoveries. So far, progress has been smooth and steady.
Already, the Wilmot SPORE team has established two new experimental drug trials, began building a blood and tissue database for research, obtained additional funding to expand a couple of particularly promising studies, initiated a new program in lymphoma epidemiology, and recruited two scientists to join the SPORE team.
“We’re very excited about the progress we’ve made and how it’s changing patient care already,” says Richard I. Fisher, M.D., director of the Wilmot Cancer Center and lead scientist on the multi-faceted SPORE program. “We’ve also built a team with a great collaborative spirit across several institutions and that’s so very important to this program.”
Offering a Second Chance
What is Lymphoma?
Lymphomas are a group of cancers that originate in the lymphatic system, which helps the body fight infection and disease.
This year, about 74,000 Americans will be diagnosed with non-Hodgkin’s lymphoma and the less common Hodgkin’s disease.
The National Cancer Institute is keenly interested in learning more about the causes and treatments of lymphomas because the incidence has grown by nearly 80 percent in the past 30 years. In New York State, Monroe County has one of the highest rates of lymphoma incidence.
The fast-track project has given a Utica-area man a second chance for survival by participating in one of the clinical trials of an agent that may inhibit development of a key protein that is found in many cancer cells.
Bible Baptist Church minister James “Douglas” Hanback travels to Rochester for treatment for T-cell lymphoma, a rare and aggressive disease that is resistant to standard therapies. When diagnosed three years ago, his oncologist Atul V. Butala, M.D., recommended he take advantage of the expertise at the Wilmot Cancer Center, which has one of the largest teams of lymphoma specialists in the Northeast.
Jonathan Friedberg, M.D., chief of Hematology/Oncology, suggested a clinical trial that brought his disease into remission for 18 months. When the lymphoma returned last summer, Hanback was offered another investigational therapy generated by the SPORE team.
“It was either the clinical trial or try some other stuff that hasn’t shown great benefit,” says Hanback, 50. “It was an easy decision. I looked at my wife and our four kids and well, there’s the motivation.”
Hanback had a “remarkable response” to the drug, which is less toxic than other chemotherapy agents, and it brought the disease into remission. Since then, he received a potentially curative bone marrow transplant in May. Recovery has been swift and he’s back to work supporting parishioners.
“It’s exciting to see a patient have a response to a new drug and the response for someone with T-cell lymphoma is very promising,” says Wilmot oncologist Steven Bernstein, M.D. He is collaborating with Arizona Cancer Center oncologist Daruka Mahadevan, M.D., Ph.D., an expert in development of new therapeutic agents, on the Phase 2 clinical trial of MLN-8237 and other projects.
“We all have different areas of expertise and we apply our skills in not just one project, but several endeavors,” Bernstein says. He is co-director of Wilmot’s lymphoma biology program.
The drug is an aurora kinase inhibitor and scientists find high levels of this protein in a variety of cancer cells, though they don’t know why. Quelling the protein is one tactic for controlling the disease, and in preclinical studies, MLN-8237 has been effective.
Given the early successes that doctors are seeing using this new therapy, the team will expand the clinical trial to patients with other forms of lymphoma. Oncologist Paul Barr, M.D., who joined Wilmot earlier this year, will assess the benefit of MLN-8237 combined with standard therapies for T-cell lymphomas.
The SPORE grant supports collaborative programs that will help bring laboratory discoveries to the clinical setting quickly and to target lymphoma cells and personalize treatments.
What is the SPORE?
The highly competitive National Cancer Institute-funded Specialized Programs of Research Excellence (SPORE) fuels translational research projects designed to quickly move research from the lab to patients.
The NCI funds SPORE projects at the top academic institutions across the country focusing on brain, breast, gastrointestinal, genitourinary, gynecologic, head and neck, ovarian, pancreatic, prostate, and skin cancers, as well as leukemia, lymphoma and myeloma.
“Holding a SPORE grant credentials the James P. Wilmot Cancer Center as a national leader for lymphoma research and care,” says Richard I. Fisher, M.D., director of the Wilmot Cancer Center. “It’s a ‘seal of approval’ from the National Cancer Institute for the research program that we’ve built.”
This five-year grant is the first for the Wilmot Cancer Center, the only upstate institution to earn prestigious SPORE funding, which is awarded to institutions conducting collaborative, novel cancer research programs. There are only four other lymphoma SPORE grants in the country, at Johns Hopkins University, University of Iowa, City of Hope and Baylor College of Medicine.
Bernstein and Arizona’s Thomas P. Miller, M.D., and Margaret Briehl, Ph.D., are working to manipulate the activity of “free radicals” at the cellular level to kill tumors. Cancer cells are more sensitive to changes in the levels of free radicals and by modulating the levels, the body’s immune system may help fight the deadly cells.
Scientists are using imexon, an investigational drug, to regulate the machinations of the cellular debris. Early, under-the-microscope analyses and results are positive, which means in the coming months, they will likely launch a clinical trial to study dosing and effectiveness in select groups of patients.
The potential that this study holds, and Bernstein’s other immune response research, caught the attention of the Leukemia and Lymphoma Society. The group recently awarded Bernstein a $600,000 grant to further his work, which brings his research funding to more than $3 million.
“This type of grant funding is one of the benefits of receiving a SPORE grant because it shows that we’re doing novel research and we receive additional funding for parallel studies as a result,” says Friedberg. “It helps us build a stronger team and to have greater impact in the laboratory and with patients.”
Among the clinical research objectives, SPORE funding is also designed to strengthen the research infrastructure for additional growth. Hematopathologist W. Richard Burack, M.D., Ph.D., is leading the creation of a tissue bank of live lymphoma cells from consenting patients.
In this age of personalized medicine and targeted therapies, the tissue bank is a valuable tool to gain understanding of lymphomas many variations at the cellular level. This state-of-the-art database is one of only a handful in the country for lymphoma.
“When you look at the very complex nature and numerous scenarios that come with lymphomas, the scientist can study these samples and get better understanding of how each tumor is unique,” says Burack, who leads a group essential to the diagnosis and staging of lymphoma, leukemia or other blood disorders.
“We’re able to provide scientists specimens that you can’t get at any other biorepository in our country because it not only includes the tumor cells, but all the material around it that shows the inflammation and immune cells around the tumor.”
For scientists like Bernstein, who is assessing immune response to disease, access to these rare samples “allows us to look at the mechanisms of novel agents on lymphoma cells.” He will rely on them as he pursues the Leukemia and Lymphoma Society-funded research into how genetic abnormalities in tumors affect treatment outcomes.
Supporting Young Scientists
Among the many advantages of bringing scientists from multiple institutions together for a project as massive as the lymphoma SPORE are the opportunities for young scientists. Leaders bring talented researchers who are building their research portfolios into the fold, mentoring them and offering seed funding for pilot projects.
“It’s a tremendous opportunity for some of our junior faculty members to join this team and learn not only from scientists throughout our Medical Center, but our partners at Arizona and Virginia too,” says Friedberg.
Jennifer Kelly, M.P.H., Ph.D., a post-doctoral epidemiology researcher, received a SPORE Career Development Grant to continue her research into the role of vitamin D and lymphoma and create a lymphoma epidemiology program.
Her doctoral research centered on whether vitamin D deficiency contributed to the development of lymphoma. “We did not find an association between vitamin D and lymphoma risk overall. However, we were unable to look within specific subtypes of lymphoma with this small preliminary study,” Kelly says.
To continue this research, she is working with scientists at Mayo Clinic in Rochester, Minn., which is leading a separate lymphoma SPORE project in partnership with University of Iowa’s Holden Comprehensive Cancer Center. Mayo Clinic has a large epidemiologic database of information on patients with lymphoma and she is tapping into their data on risk factors, treatments, and survival to further her project.
Her grant funding will support efforts to build a parallel database here at URMC to expand opportunities for analyses and greater collaboration.
“Working in parallel with the SPORE tissue bank, we want to also gather epidemiologic information, such as exposure to potential risk factors and demographic characteristics, and follow lymphoma patients during and after treatment to evaluate factors that might be associated with treatment responses, quality of life and survival,” says Kelly, who studied epidemiology with Susan G. Fisher, Ph.D., chair of Public Health Sciences. Fisher is leading the Career Development Program within the SPORE initiative with Briehl from Arizona.
“Jennifer Kelly is a great example of how the Career Development Program is effective,” Friedberg says. “She earned her degree in epidemiology and was looking at her options to pursue and we were able to provide her with funding and mentorship that made joining our team to study lymphoma and expand our program so very attractive for her.”
Scientists have three more years to execute the NCI-funded research and hope to continue the work with a grant renewal.“The beauty of the SPORE grant is that our patients reap the many rewards of the studies and the additional research projects that blossom from it,” Fisher says. “It takes a lot of hard work and the successes we’re seeing are very satisfying for all of us.”