Maintaining Momentum: Pelotonia Idea Grants Help Discoveries Happen
Cancer research is a process. A researcher or physician-scientist makes an observation in the laboratory or clinic, then asks, “Why did that happen?” Or, “How can we improve that?” He or she will gather with colleagues and develop a hypothesis that answers the question. Then they will conduct experiments to test their hypothesis.
That’s how discoveries are made. It’s how we build a cancer-free world. That is, if the researchers have financial support for their work.
Federal funding for cancer research has fallen annually since 2006. Grants are fewer in number, smaller in amount and more difficult to obtain. Furthermore, the more novel the idea, the more difficult it is to compete for funding—big ideas hold great promise but often lack the data needed to compete for scarce dollars. It’s a paradox: Exciting ideas need data to obtain funding, but funding is needed to obtain the data.
Idea Grants funded by Pelotonia break that cycle at the OSUCCC – James. In fiscal 2014, 20 Pelotonia Idea Grants have been awarded to innovative projects developed by OSUCCC – James investigators. Three of those projects are described here (to read about the other Idea Grants, visit https://cancer.osu.edu/pelotonia).
Loneliness and Breast Cancer Development and Progression
Breast cancer is the second-leading cause of cancer death among women in the United States and worldwide. Studies have shown that women with weak social networks have worse treatment outcomes than women with strong social support.
A Pelotonia Idea Grant has been awarded to a team of OSUCCC – James researchers to test their hypothesis explaining how this happens.
The study, which focuses on a gene that normally protects the body against cancer, is led by OSUCCC – James breast-oncologist Maryam Lustberg, MD, MPH, director of Breast Cancer Survivorship at the Stefanie Spielman Comprehensive Breast Center; Courtney DeVries, PhD, professor of Neuroscience and of Psychology who specializes in links between social behavior and health; and Cynthia Timmers, PhD, director of the Solid Tumor Translational Science Shared Resource at the OSUCCC – James.
This gene, called PTEN, is often inactivated in breast cancer.
In mice, reducing the activity of this gene by 20 percent makes the animals more susceptible to cancer development. Animal studies by the OSUCCC – James researchers suggest that social isolation can reduce PTEN activity by 50 percent.
The researchers hypothesize that levels of a hormone called oxytocin, which is released during social interaction, drop when mice are socially isolated. That reduces the activity of the PTEN gene in mammary tissue and makes mice more susceptible to cancer development.
Their Pelotonia Idea Grant will help the researchers learn whether a similar association exists between social isolation and PTEN activity in humans. The study will recruit 100 women undergoing breast biopsy at The Spielman Center.
The researchers will establish the women’s social networks using questionnaires and test the breast tissue for PTEN activity. They also will test whether PTEN levels in skin reflect the gene’s levels in breast tissue. If so, it might mean that a simple skin sample can be used to gauge PTEN activity in breast tissue in future clinical trials.
“This study could help us understand individual differences in breast-cancer susceptibility and progression, which could lead to new diagnostic, therapeutic and prognostic tools for breast cancer prevention and treatment,” Lustberg says.
She notes that the results might also apply to endometrial, thyroid, prostate, brain, pancreatic and colon cancers, which are also influenced by PTEN.
The Right Therapy for the Right Glioblastoma Patient
Glioblastoma (GBM) is the most common and lethal form of brain cancer in the United States. Even with aggressive therapy, patients survive only 15 months on average.
Recent research has shown that molecular changes in some GBM tumors correlate with treatment outcomes. It raised the hope that treating the disease with drugs targeting these changes would extend patients’ lives.
But the drugs have not helped as expected, in part because new methods are needed to accurately identify GBM progression and the molecular targets that identify patients for personalized therapy.
A Pelotonia Idea Grant is helping a team of OSUCCC – James physicians and researchers in neuro-oncology, neurosurgery, neuropathology and engineering to pool their expertise and help develop those techniques.
The research team includes neuropathologist Jose Otero, MD, PhD; biomedical Informatics and image analysis specialist Metin Gurcan, PhD; director of Neuro-oncology at Ohio State and the OSUCCC – James Vinay Puduvalli, MD; neurosurgeon Brad Elder, MD; and associate professor of Chemical and Biomedical Engineering Jessica Winter, PhD.
They are developing strategies to improve diagnostic accuracy of GBM, including innovative digitized-image-analysis techniques that distinguish false tumor progression from true progression.
“We are harnessing technology to improve the treatment of an intractable and deadly form of cancer,” says Elder. “Our study is building a new approach to tissue analysis that has great potential for use in clinical trials and possibly with other types of tumors.”
“Targeted therapy for cancer will be the standard treatment of the future, and it will lead to the control and, eventually, to the cure of cancers,” says Puduvalli. “However, efforts at consistently identifying the targets—there may be more than one in a single tumor cell—has hit a roadblock because currently available tests lack the precision to accurately detect such targets,” he adds. “Our study will bring a next-generation technology to the fight against cancer and a new level of accuracy to the detection of cancer targets.”
The Pelotonia-funded study will also generate critical data needed to apply for external grant funding, and it will ultimately help develop new techniques to personalize the therapy and guide the management of GBM patients.
Targeting Oncogenes for New Liver Cancer Therapies
Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer. Worldwide, it caused an estimated 746,000 deaths in 2012, making it the second-leading cause of cancer death. The disease is usually associated with hepatitis, fibrosis, cirrhosis and other liver diseases.
Liver cancer mortality is high because the disease lacks effective therapy. “The liver works to clean toxins from the blood, making it challenging to develop drugs that can penetrate the liver and reach cancerous cells,” says Kalpana Ghoshal, PhD, associate professor of Pathology. Ghoshal was awarded a Pelotonia Idea Grant to investigate a strategy for treating HCC.
Research by Ghoshal and others has shown that a molecule called microRNA-122 (miR-122) is critical for normal liver function and that it protects against cancer. Cancerous liver cells often stop producing this molecule, an event that is associated with poor prognosis, tumor recurrence and metastasis.
Animal studies by Ghoshal have shown that restoring miR122 in liver cancer cells causes the malignant cells to die. Normally, miR-122 suppresses the activity, or expression, of two genes that play an important role in cell proliferation. When liver cells lose miR-122, those two genes become much more active, contributing to tumor growth.
Ghoshal is investigating whether use of a targeted drug to block either of the two cancer-promoting genes, plus a drug that restores miR-122 levels, will inhibit liver cancer growth and offer a potentially effective therapy for the disease.
“Results from these studies could lead to a phase I clinical trial in liver cancer patients of two experimental drugs in combination with miR-122 for treating a human cancer,” Ghoshal says.