APRIL 23, 2015 — Two powerhouses of cancer support — the American Association for Cancer Research (AACR) and the Pancreatic Cancer Action Network (PanCAN) — have jointly awarded Georgetown Lombardi Comprehensive Cancer Center and Thomas Jefferson University in Philadelphia $1 million over three years to determine whether molecularly tailored treatment for pancreatic cancer improves survival compared with the current standard of care.
“Pancreatic cancer is one of the few cancer types for which death rates are steadily increasing; it is projected to become the second leading cause of cancer-related death in the United States by 2030,” says Margaret Foti, PhD, chief executive officer of the AACR. The award recognizes “the urgent need for research into this deadly disease,” she says.
To that end, Georgetown Lombardi and Thomas Jefferson University are teaming up to conduct the first clinical trial that will compare standard of care chemotherapy with molecular tailored therapy.
Tailored Therapy Studied
Georgetown Lombardi oncologist and researcher Michael J. Pishvaian, MD, PhD, who co-leads the grant, says the trial will be the most comprehensive investigation to date of individualized therapy for pancreatic cancer.
“We have a dire need to develop new molecularly targeted therapies for pancreatic cancer, which is aggressive and difficult to successfully treat,” says Pishvaian. “This study will give us great insights into new therapies that might make a significant difference.”
There are likely several key molecular abnormalities driving individual patients’ cancers. But every patient’s tumor is different, and clinical trials group all patients together to test a novel therapy — irrespective of the unique characteristics of that patient’s tumor, he says. “Therefore, any potential promising results get diluted because novel therapies are not administered to those select patients who are most likely to respond, based on their tumors’ molecular profile. In this trial, we have the opportunity to treat every patient as unique, and to tailor each one’s therapy to each one’s tumor characteristics.”
How the Study Works
The 60-patient randomized study, expected to begin later in 2015, will be conducted at five centers — Georgetown Lombardi, Cedars-Sinai in Los Angeles, Virginia Mason in Seattle, Mount Sinai in New York, and Thomas Jefferson University, with major scientific contributions from Emmanuel F. Petricoin, PhD, at George Mason University in Virginia.
A biopsy of each patient’s cancer will be screened for 600 genes as well as protein expression to uncover molecules and pathways that are driving the cancer and to predict a patient’s response to chemotherapy or other tailored therapy.
Once these analyses are completed, a “tumor board” of researchers and oncologists will help decide which therapies might work best for each individual patient.
“We are eager to immediately enhance patient outcomes by incorporating candidate and novel predictive tumor biomarkers into therapeutic decision making, making treatment rational and realistic,” Pishvaian says.
A Deeper Understanding
The research team will use novel laboratory techniques to further understand what is happening within each cancer biopsy, and how individual tumors will respond to therapy.
For example, Christopher Albanese, PhD, one of the co-leaders, will spearhead an effort at Georgetown Lombardi to develop conditionally reprogrammed cells (CRCs) for each patient’s tumor. CRCs, which were developed at Georgetown Lombardi, can keep both normal and cancerous cells alive indefinitely, allowing researchers to predict how therapies will work. In parallel, Georgetown Lombardi’s Stephen Byers, PhD, will grow the patient tumors in a novel “avatar” — zebrafish, to be used as a surrogate to predict response and determine resistance pathways.
Cancer modeling will be directed by the grant’s other co-leader, Jonathan R. Brody, PhD, of Thomas Jefferson University, and will include Subha Madhavan, PhD, director of clinical research informatics at Georgetown Lombardi and director of the Innovation Center for Biomedical Informatics at Georgetown.
“In the end, it may turn out that patients will do best with standard chemotherapy, and this is the only way to know if that is true — or if molecularly tailored therapy identifies more effective options,” says Pishvaian.
By Renee Twombly