From Ideas to Impact
Discoveries Made With Pelotonia Support
Pelotonia funds help support groundbreaking preliminary studies at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James). These studies produce data and publications that can lead to grants for larger studies. In this way, Pelotonia helps advance cancer treatment and improve patient care. Here are three examples of that work.
Predicting a Skin Cancer’s Spread
About 700,000 cases of cutaneous squamous cell carcinoma (cSCC), a form of skin cancer, are diagnosed annually in the United States. Most of the time, the disease is curable. But in about 5 percent of cases, the cancer spreads to other areas of the body – it metastasizes – causing up to 8,800 deaths per year.
There is no way for doctors to predict the patients in which the disease might spread, and there are no FDA-approved targeted therapies for treating metastatic cSCC.
In 2011, Amanda Toland, PhD, associate professor of Cancer Biology and Genetics, was awarded a Pelotonia Idea Grant for a study designed to identify genomic changes that cause squamous cell skin cancer to metastasize. The findings could contribute to the development of therapies for treating these aggressive tumors.
Her research led to two papers. In one, Toland and her collaborators compared levels of molecules called microRNAs that were present in metastatic cSCC tumor cells relative to cSCC cells from the initial tumor. The researchers identified several microRNAs that were present at significantly higher levels in the metastatic cSCC cells. “These microRNAs may be useful as biomarkers for identifying tumors that might metastasize or as potential therapeutic targets,” Toland says.
In a second study, Toland and her colleagues used gene sequencing to identify gene mutations found in metastatic cSCC cells compared with cSCC cells from the primary tumor. That study found two genes in particular that were mutated much more often in metastatic cSCC cells.
Toland hopes to confirm the microRNA findings in a larger study, and to determine the biological role of the mutated cSCC genes. She believes her findings will eventually contribute to improving the treatment of metastatic cSCC.
Preparing for Resistance
A 2014 Pelotonia Idea Grant helped Sameek Roychowdhury, MD, PhD, learn how lung, bladder, breast and other cancers could develop resistance to a new class of targeted drugs called fibroblast growth factor receptor (FGFR) inhibitors. The team is involved in three different clinical trials for FGFR inhibitors, including a trial led by OSUCCC investigators.
Roychowdhury and his collaborators used a laboratory model to show how cancer can evade these agents. “Our findings also provide insights into how clinical trials for these therapies could be further developed to overcome the problem of drug resistance,” he adds.
Examining other molecules in the FGFR pathway, the researchers found that a regulatory protein called Akt remained highly active, even when FGFR is blocked by an FGFR inhibitor. Akt is a key regulator of cell biology, and it is directly involved in cell proliferation, cell survival and cell growth.
Furthermore, they found that using a second targeted drug to block Akt, along with an FGFR inhibitor, could significantly slow cell proliferation, cell migration and cell invasion in the lung cancer and bladder cancer cells. “FGFR inhibitors are new therapies being developed in clinical trials for patients whose cancer cells have genetic alterations in this family of genes,” Roychowdhury says. “We believe our findings will help improve this therapy for lung, bladder and other cancers.”
Developing a Blood Test to Detect Lung Cancer Early
Lung cancer is a leading cause of cancer death worldwide. It’s expected to kill nearly 156,000 Americans alone this year. Lung cancer causes so many deaths in part because it is difficult to detect early. Consequently, it is generally diagnosed at a late stage of disease, when a cure is difficult.
In 2013, L. James Lee, PhD, professor of Chemical and Biomolecular Engineering, and a team of OSUCCC – James researchers were awarded an Idea Grant to support preliminary studies on a high-tech way to detect lung cancer early using a blood sample.
Their innovative project tested the feasibility of using a low-cost technology called a tethered lipoplex nanoparticle (TLN) biochip for detecting signs of lung cancer in the bloodstream. TLN essentially consists of molecular probes encapsulated in nanoparticle complexes that are tethered to a biochip. The biochip sits on a glass microscope slide.
The tethered nanoparticle complex is designed to capture submicroscopic vesicles called exosomes and detect certain molecular RNA targets. The tiny vesicles are given off by cancer cells and are found in a patient’s blood. They contain molecules called messenger RNA (mRNA) and microRNA that can serve as a signal for lung cancer.“
Initial testing of the tethered lipoplex nanoparticle biochip for detecting lung cancer has been promising,” Lee says. “If this new method proves reliable and practical, it may also be applicable to other cancers and to viral infections.”
The findings from the Idea Grant study led to three published papers and a federal grant.