The Stefanie Spielman Fund for Breast Cancer Research supports scientific studies that can be translated to innovative patient care at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James). Some of the most talented and experienced researchers in the world are working to find cures for breast cancer at the OSUCCC – James, and all of them share Stefanie’s dream of a cancer-free world.
With help from the Spielman Fund, these researchers are creating drugs and developing therapies that bring their ultimate goal of ending cancer closer to reality. Herein, some of these scientists explain their research and how they are assisting in the global battle against breast cancer – a battle we are all fighting with Stefanie in mind. As you read about their remarkable work, remember that it would not be possible without the generous support of caring people like you.
The Spielman Fund helps OSUCCC – James scientists advance breast cancer research in numerous ways, including:
• Creation of a Tissue Archive Services and Tumor Bank – collections of healthy and cancerous breast tissue samples that scientists can use for comparison and analysis to uncover elements of cancer formation and develop more successful treatments.
• Development of sophisticated imaging technologies that detect cancer earlier when it can be more effectively treated.
• Identification of treatment targets and the development of drug-therapy regimens that can save lives and give patients a higher quality of life.
Targeting Triple-Negative Breast Cancer
Charles Shapiro, MD, director of Breast Medical Oncology and leader of the breast cancer research program at the OSUCCC – James, says the Spielman Fund helped make the Spielman Breast Cancer Tissue Bank possible.
“This invaluable resource provides thousands of breast cancer samples from women who received care at The James, along with the types of treatments they received and the results of their outcomes,” says Shapiro, a professor of Internal Medicine at Ohio State and member of the Cancer Control Program at the OSUCCC – James.
The Tissue Archive Services and the Tumor Bank allow for promising genes or proteins that are discovered in the laboratory using cell lines or animal models to be quickly tested for their importance and relevance to human breast cancers that come from patients.
Examples of research conducted using these resources include the molecular factors associated with estrogen receptor-negative, progesterone receptor-negative and HER-2 negative (or “triple-negative”) breast cancers, and the molecular factors associated with tamoxifen resistance. Triple-negative breast cancer (TNBC) accounts for about 15 percent of all breast cancers and has few treatment options.
OSUCCC – James research teams have made important discoveries relating to TNBC using these banks, and their work has led to grants from the National Cancer Institute to further support the research.
One large-scale study supported by NCI grants and the Spielman Fund showed that small molecules called microRNAs can be used to define four subtypes of TNBC. The study, led by Shapiro and Kay Huebner, PhD, along with collaborators in Italy, could lead to new screening methods, prognostic markers and targeted treatments for this often-fatal cancer.
“Treating women with triple-negative breast cancer is challenging because this malignancy can be very different genetically from one patient to another,” Shapiro says. “We believe these microRNA signatures define novel subsets of triple-negative breast cancer and offer new insights into the biology of the disease and better ways to treat patients.”
“These findings strongly suggest that microRNAs play an important role in TNBC and might be used to better identify the most effective treatment for a patient’s tumor,” adds Huebner, a professor of Molecular Virology, Immunology and Medical Genetics at Ohio State who is also a member of the Molecular Biology and Cancer Genetics (MBCG) Program at the OSUCCC – James. “MicroRNAs can help us improve and personalize therapies for individual patients.”
In another study of TNBC supported by the Spielman Fund, Erin Macrae, MD, an assistant professor of Medical Oncology, is working to determine whether inhibiting the action of a pair of proteins will improve outcomes for patients with triple-negative disease.
“Our study at Ohio State will be the first phase II clinical trial to evaluate a novel therapeutic strategy for patients with metastatic TNBC,” says Macrae, who also is a member of the Experimental Therapeutics Program at the OSUCCC – James.
Ching-Shih Chen, PhD, a professor of Medicinal Chemistry and Pharmacognosy at Ohio State, and his team are developing several new drugs that target triple-negative breast cancer. Their goal is to stop the disease from spreading, eradicate cancer stem cells and enhance the effectiveness of current therapies.
“In collaboration with Dr. Shapiro, our research focuses on developing new therapeutic strategies to enhance the outcomes in these patients,” says Chen, a member of the Molecular Carcinogenesis and Chemoprevention Program at the OSUCCC – James.
Chen and colleagues are trying not only to find therapeutic agents that kill TNBC cells, but to reduce the metastatic capability and stem cell population of these cells. Chen’s team is working with different agents that can slow aggression and eliminate chemoresistance in these cells.
“With support from the Spielman Fund, we have developed drugs that target different molecular defects in cancer, which enhances current treatment, slows the progression and prevents the recurrence of the disease,” says Chen, noting that these drugs are in preclinical development.
Targeting Chemo Brain
Spielman Fund revenue also helped a team of Ohio State researchers generate preliminary data that led to an Idea Grant from Pelotonia, the annual grassroots bicycle tour that raises money for cancer research at the OSUCCC – James, to help them study a possible cause and treatment for chemotherapy-induced cognitive deficits.
Nearly a third of breast cancer patients who receive chemotherapy report problems with memory, concentration, attention and understanding during and after treatment. Sometimes called “chemo brain,” these deficits can also be a problem for patients treated for other malignancies, including ovarian and prostate cancers. The cause is poorly understood, and there is no treatment.
But Maryam Lustberg, MD, assistant professor of Medical Oncology at Ohio State and a member of the Cancer Control Program at the OSUCCC – James, and Courtney DeVries, PhD, professor of Neuroscience and Psychology at Ohio State, have evidence linking these cognitive difficulties to the overactivity of a type of immune cell in the brain. They have also identified an anti-inflammatory drug called minocycline that might calm the overexcited cells and ease the symptoms.
“Our data from an animal model suggest that certain chemotherapy can overactivate brain cells called microglia, and that this contributes to localized inflammation and changes in brain cells,” Lustberg says, noting that microglia are involved in neurological disorders such as multiple sclerosis and other neuroinflammatory conditions. “But we believe we are the first to tie them to chemotherapy-induced cognitive deficits.”
Targeting Cancer Tumors
The laboratory of Michael Tweedle, PhD, a professor of Radiology who holds the Stefanie Spielman Chair in Cancer Imaging and is a member of the Experimental Therapeutics Program at the OSUCCC – James, has developed a drug that not only detects cancer but also treats it with a radioactive isotope, Lutetium-177, upon discovery.
“It’s like a dirty bomb. It kills cancer within just a small space—a millimeter or two,” says Tweedle, who adds that this work is continuing with “an improved version of the drug that has fewer side effects and stronger tumor localization.”
Tweedle also is making Optical Surgical Navigation imaging agents designed to reduce positive margins after breast cancer surgery. “These agents use the same kind of ‘bloodhound’ targeting peptide, but with both a PET imaging radiolabel and a second label that emits a fluorescent light that the surgeon can see on a video screen above his or her surgery,” he explains.
There is always a need for drugs to treat cancers that have escaped initial diagnosis and evaded treatment. Tweedle’s innovative work offers a lifesaving opportunity for patients and provides a model for other labs around the world to utilize.
Another important area of study in the search for new breast cancer treatments involves microRNA molecules, which help cells control the amount and kinds of proteins they make. Abnormal levels of certain microRNAs are a hallmark of many cancers.
A study led by researchers at the OSUCCC – James, and supported in part by the Spielman Fund, suggests that an experimental drug known as AS1411 can reduce breast cancer aggressiveness, reverse resistance to a drug called fulvestrant and perhaps improve the effectiveness of other breast cancer drugs. Findings from this study suggest a new strategy for treating breast cancer.
Specifically, AS1411 inhibits a protein called nucleolin that plays a critical role in the microRNA maturation process. “This study of the role of nucleolin in microRNA regulation has clear clinical implications,” says Carlo Croce, MD, principal investigator for this study and director of human cancer genetics at Ohio State. Croce also is a member of the MBCG Program at the OSUCCC – James.
First author Flavia Pichiorri, PhD, assistant professor in the Division of Hematology at Ohio State and a member of the MBCG Program at the OSUCCC – James, notes that nucleolin is a promising therapeutic target for microRNA modulation in cancer cells. “To our knowledge,” she says, “this is the first large study to show a clear association between nucleolin and specific microRNAs that are causally involved in cancer.”
Our vision at the OSUCCC – James is to create a cancer-free world, a vision that Stefanie Spielman shared. The advancements in breast cancer research and care outlined in this newsletter will benefit not only the people of central Ohio but everywhere by contributing to the global cause against this disease. Even better, improvements in breast cancer treatment will be translated to the care of patients with other forms of this devastating disease. Thanks to your support, we are coming ever closer to realizing our shared vision while offering hope to millions.