Adam Wolfe, MD, PhD, Terence Williams, MD, PhD, and their team at The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute (OSUCCC - James) are conducting research to discover novel microRNA (miRNA) signatures that could guide radiation treatment decision making when caring for pancreatic cancer patients. They are also testing whether a specific miRNA could help make pancreatic cancer cells more vulnerable to radiation therapy.
Q&A with Adam Wolfe, MD, PhD, and Terence Williams, MD, PhD
Why is more personalized treatment needed for pancreatic cancer?
Pancreatic cancer is a devastating disease with dismal survival rates and high morbidity due to local tumor progression, distant tumor progression, and toxicities from current therapies including chemotherapy and radiation. Currently, patients with locally confined disease are treated with multi-regimen chemotherapies and surgery, if possible. The use of radiation therapy either before or after surgery is more controversial, and there are no clinically-useful biological markers to help guide which patients would benefit the most from intensified local therapy with radiation. Ideally, molecular tools will allow selection of those patients who have a higher risk of having local tumor recurrence and therefore might benefit most from radiation. Conversely, such biomarker tools could spare patients at low risk the potential side effects of radiation. To do this, we need to develop improved biological signatures from tumors to help guide our treatment decision-making process.
What are microRNAs (miRNAs) and why did you choose to focus your research on them?
microRNAs (or miRNAs) are small strands of RNA that do not encode any protein but are a cellular regulator mechanism. These miRNAs target genes with complimentary binding sequences. There are over 800 known miRNAs and each of these individual miRNAs can target multiple genes to “switch off” translation and subsequent protein expression. These miRNAs are a great tool to study for biomarker research since they are relatively stable and can be recovered from stored tumor tissue decades later. Also, miRNAs in cancer cells have different miRNA expression profiles compared to normal cells. Even within the same cancer types, certain more aggressive-behaving tumors can have different miRNA expression profiles.
How could your research help improve outcomes for patients with pancreatic cancer?
We hope that our research will lead to novel biomarker signatures that can be further validated in larger patient studies that will ultimately guide individual treatment decisions to personalize the treatment of pancreatic cancer. As an added benefit to our work, we hope to identify specific miRNAs that can serve as targets for the treatment of pancreatic cancer.
What progress have you made to date?
We have published the first study from our work demonstrating that a 4-miRNA signature can predict outcomes for resected pancreatic cancer patients. This study was developed at OSUCCC - James and was validated on two independent pancreatic cancer cohorts. We have now started generating newer data from three large National Cancer Institute (NCI)-Designated Cancer Centers that will lead to development of a novel miRNA signature that will accurately predict outcomes for patients who receive chemotherapy and chemoradiation treatment both before and after surgery. Laboratory experiments are also ongoing to evaluate the role of certain miRNAs in radiation or DNA damage response through our profiling efforts.
Why is the grant from the ROI important to your research?
The support from ROI has been critical for the success of these studies. Without the generous support from this grant, we would not have been able to perform the profiling of hundreds of patient samples critical for these types of biomarker studies. In addition, support from the ROI will hopefully lead to identification of novel miRNA or molecular pathway targets for the treatment of pancreatic cancer. Finally, the data generated from these studies will serve as the basis for future grant applications requesting more support to extend this work.