Clinical trials

Bench to Bedside and Back: How Laboratory Findings Lead to Clinical Trials

The Pancreatic Cancer Action Network will proudly devote over $3.7 million to funding research grants in 2012, and also strongly advocates for increased pancreatic cancer research dollars from the federal government. Additionally, the Pancreatic Cancer Action Network encourages all patients to consider clinical trials when exploring their treatment options. But – how does research progress in the laboratory turn into patient benefit? Following is one story that illustrates how scientists can take what they learn in the laboratory and translate it to develop a clinical trial for patients.

When Scientific Advisory Board Chair Dave Tuveson, MD, PhD was funded by his Pancreatic Cancer Action Network Career Development Award in 2003, he was able to develop the first mouse model of pancreatic cancer that mimics the progression of human disease. Importantly, Dr. Tuveson’s mice showed poor responsiveness to gemcitabine, the standard of care for pancreatic cancer patients, in a way that mirrored human patients’ response to the drug.

Further analyses by Ken Olive, PhD (recipient of the 2011 Tempur-Pedic® Retailers – Pancreatic Cancer Action Network – AACR Career Development Award), conducted when he was a postdoctoral fellow with Dr. Tuveson, showed that the dense microenvironment surrounding the pancreatic tumor contributes to the resistance of the mice to gemcitabine. In fact, the microenvironment was so thick and impenetrable that the drug could not even make it to the cancer cells themselves.

When Drs. Olive, Tuveson, and colleagues looked more carefully at the individual cells comprising the microenvironment, they found that a cell signaling pathway called hedgehog was abnormally activated, while hedgehog signaling is not supposed to be active in healthy adult cells. Because of this observation, clinical trials are currently underway to test the combination of a novel inhibitor of the hedgehog signaling pathway and gemcitabine. The hope is that hedgehog inhibition (blocking the pathway) will break down some of the dense microenvironment surrounding the cancer cells, leaving them vulnerable to attack by gemcitabine.

In this example, a clinical observation (that pancreatic cancer patients respond poorly to the chemotherapy drug gemcitabine) was recreated in an accurate mouse model of the disease. The mouse model provided insight into a potential mechanism for drug resistance (that the drug isn’t being properly delivered to the tumor), and analyses of the tissue specimens in the laboratory revealed activation of a pathway that can be therapeutically targeted. Put together, these medical and scientific findings have led to a promising, strategic treatment option for one of the most difficult cancers to treat.

The Pancreatic Cancer Action Network recommends that all patients consider clinical trials when looking at their treatment options. Without clinical trials, patients will not have access to cutting edge research and we will not develop new, better treatment options for pancreatic cancer. Increasing patient participation in pancreatic cancer clinical trials is an extremely important part of the research process. This is why the Pancreatic Cancer Action Network has a proprietary, searchable database that houses information about all of the pancreatic cancer clinical trials taking place in the U.S. Ensuring that patients understand their treatment options and enroll in clinical trials is just as important as funding research in a laboratory. For information about clinical trials or for a personalized clinical trials search, please call our Patient and Liaison Services (PALS) program toll-free at 877-272-6226 or email pals@pancan.org. PALS Associates are available M-F 7am-5pm Pacific Time.

Click here to read an interview with Pancreatic Cancer Action Network Medical Advisory Board Chair, Jordan Berlin, MD, discussing the importance of participation in Phase III clinical trials.