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. So far, in 2014, nine 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 http://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 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, focuses on a gene that normally protects the body against cancer.
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 Ohio State’s Stefanie Spielman Comprehensive Breast Center. The researchers will establish the women’s social networks using questionnaires, and they will test the breast tissue for PTEN activity. The researchers will also 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 particular molecular changes in some GBM tumors correlate with treatment outcomes. It raised the hope that treating the disease with drugs that target 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 the OSUMC and OSUCCC – James Vinay Puduvalli, MD; neurosurgeon Brad Elder, MD; and associate professor of Chemical and Biomedical Engineering Jessica Winter, PhD.
They are developing new strategies to improve diagnostic accuracy of GBM, including innovative digitized-image-analysis techniques that accurately 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 study will also generate critical data needed to apply for external grant funding. The Pelotonia-funded study will ultimately help develop new techniques to personalize the therapy and guide the management of GBM patients.
TARGETING ONCONGENES 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 miR-122 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.
PELOTONIA HELPS PHYSICIANS PURSUE PASSION FOR ENDING CANCER
Apart from caring for his wife Kari and their six children, defeating cancer is the life-passion of Theodoros (Ted) Teknos, MD.
After seeing how much Pelotonia contributes to that goal, he is compelled to do his best every year as a rider in the annual grassroots bicycle tour.
“Since it started in 2009, I have participated in every Pelotonia tour as a rider on Team Head and Neck (a part of Team Buckeye, Ohio State’s official superpeloton),” says Teknos, professor and vice chair of the Department of Otolaryngology – Head and Neck Surgery, and director of the Division of Head and Neck Surgery, at Ohio State.
He always rides the full 180-mile circuit and annually attains the event’s “high roller” status for raising at least $4,000.
“I will ride until I drop,” Teknos says. “And then I will be a virtual rider.”
He admits that, before Pelotonia, he was not an avid cyclist. In fact, he hadn’t ridden a bike at all since he was a teen.
“I stopped riding bikes when I got my first car,” Teknos says. “I picked it up again for Pelotonia, and now I am hooked.”
Finding his way back didn’t take long.
“It was remarkably easy to get reacclimated; it was like riding a bike!” he grins. “The camaraderie of preparing with my James family made it fun.”
As each event draws nearer, he keeps to a rigorous training regimen.
“I start riding in earnest in April, primarily on weekends,” Teknos explains. “Then I step it up in the summer and take a weeklong vacation to train in July.”
His wife also rides with him. “It’s a great family activity,” he says.
Teknos’ dedication to training for Pelotonia is all the more amazing in light of his demanding workload as a cancer clinician and researcher at Ohio State, where he also holds the David E. Schuller, MD and Carole Schuller Chair in Otolaryngology, and is a member of the Translational Therapeutics Program at the OSUCCC – James.
His clinical interests include head and neck cancer, head and neck benign neoplasms, skull-base surgery, microvasculature reconstructive surgery, and thyroid and parathyroid surgery.
His research focuses on cancer stem-cell biology, cancer cell signaling, predictors of treatment response, and prevention of cancer metastasis (spread).
Teknos believes everyone who works at the OSUCCC – James benefits from Pelotonia funding, because a significant share of the money is used to recruit and retain some of the top minds in cancer research and care.
“Pelotonia funds bring tremendous new scientists to our institution, some of whom I have recruited,” he says.
Teknos considers Pelotonia “a life-changing experience.”
“There are few times in life when you know you are participating in an event that is pure and good,” he says.
“By taking part in Pelotonia, you really feel the generosity and power of our community.”
|PELOTONIA HELPS PHYSICIANS PURSUE PASSION FOR ENDING CANCER|
In the 1980s it took 10 years for a scientist to study one gene. Today, scientists can study 20,000 genes in a week. That change emerged during Sameek Roychowdhury’s medical training and sparked his interest in genomics and its potential for treating cancer based on the gene changes in a patient’s tumor.
“Currently, it costs $5,000 to $10,000 to sequence all of a patient’s genes,” Roychowdhury says. “It’s not cheap but it’s feasible, and Pelotonia has helped us make genomics-based cancer medicine happen here at Ohio State.”
Sameek Roychowdhury, MD, PhD, is a physician-scientist and medical oncologist who specializes in cancer genomics, genomics-driven cancer clinical trials, and precision cancer medicine. This year he will take to his bike as he has for the past three years to ride in Pelotonia to support Ohio State cancer research.
“Pelotonia is an amazing event that grew in just a few years to become the largest bike ride in the nation for cancer research,” he says.
Roychowdhury pedals the full 180-mile route both for patients who might benefit from his research and for personal reasons. “My mother-in-law was a breast cancer survivor, and my father was a prostate cancer survivor,” he says.
He organized a peloton that includes much of his lab. Last year, the team raised $10,000, with $5,000 coming from T-shirt sales alone. This year, the T-shirts are $20, and 100 percent of the proceeds go directly to Pelotonia. The message they carry plays off the Ohio State/Michigan rivalry: “Two Goals: Beat Michigan, Beat Cancer.”
Roychowdhury notes that a portion of the dollars raised by Pelotonia supports high-risk, high-reward research. “That’s one way Pelotonia is making a difference,” he says. “High-risk, high-reward research can more rapidly advance progress against cancer.”
Pelotonia funds helped recruit Roychowdhury and other researchers who specialize in precision cancer medicine, which relies heavily on genome sequencing and sophisticated equipment. “Pelotonia funding has been crucial in bringing that technology to Ohio State and in making genomics available to patients,” he says.
Using genomic sequencing to characterize a patient’s tumor enables physician-researchers at the OSUCCC — James to choose a clinical trial that is appropriate for that particular patient based on the molecular changes in his or her tumor. “It enables us to get the most effective treatment to the patient while also facilitating drug development,” he says.
There are many ways to participate in Pelotonia and work toward the goal of ending cancer, Roychowdhury notes. “Anyone can contribute as a rider, a virtual rider, a volunteer or a supporter.
“One of the most exciting things about the event is the support of people in Ohio. You’re riding through the countryside; the houses are hundreds of yards apart; it’s the middle of the summer and hot – and you see people sitting in lawn chairs beside the road, offering lemonade, cookies and cheering us on because we are all on the ride together.
“The kind of effort that people have put into this goal of ending cancer is magical.”