Institute Develops Fresh Bench-to-Bedside Model Through Community Ties

Dario C. Altieri, MD

Director

Executive Vice President

Chief Scientific Officer

Robert and Penny Fox Distinguished Professor

The Wistar Institute Cancer Center

In more than 40 years as a National Cancer Institute (NCI)-designated cancer center—and the first center in the network devoted purely to basic research—The Wistar Institute has built a reputation for furthering the sort of scientific research that will improve clinical cancer medicine.

Traditionally, we have done this by partnering with large academic medical centers and biotech giants in order to develop new drugs or clinical tests. In recent years, however, we have learned that our best hope for making a difference in cancer may rest in community clinical medicine. Case in point: our partnership with the Helen F. Graham Cancer Center, an NCI-selected Community Cancer Center Program that is part of the Christiana Care Health System in Delaware.

By connecting Wistar researchers with Graham Center doctors, we believe we can advance our understanding of cancer biology while providing access to new therapeutic trials to a community. The Wistar-Christiana Care partnership has led to great progress in accessing patient samples for a variety of disease types, including ovarian cancer, lung cancer, head and neck cancer, and melanoma.

NSCLC Blood Test Advances

Perhaps the strongest example of this success is the development of a blood test for non-small cell lung cancer (NSCLC), created through the collaboration of Wistar professor Louise C. Showe, PhD, with her Graham Center colleagues. Showe’s 29-gene panel uses blood-based markers to predict NSCLC, a technique that was developed in her laboratory and further validated through access to patient samples. Lung cancer remains the primary cause of cancer-related death, in part because there is currently no efficient way to screen people at an early stage. In recent studies, Showe demonstrated the possibility of detecting early-stage NSCLC by taking a snapshot of gene activity in blood-borne immune cells and looking for genes involved in ERK/MAPK signaling, T-cell receptor signaling, CD28 signaling in T helper cells, and other abnormalities that are more significantly associated with NSCLC.

The collaboration allowed Showe to secure a $1 million grant from Pennsylvania’s Commonwealth Universal Research Enhancement (CURE) Program to analyze blood samples taken from patients with NSCLC at the Graham Cancer Center. By October 2013, more than two-thirds of the 600-patient accrual goal had been met, and the study is on track to reaching completion sometime in the middle of 2014.

Treatment-Naïve Samples Needed

About 85% of oncology care is given in the community at places such as the Helen F. Graham Cancer Center. Wistar researchers do not see patients in the traditional sense, of course, but this is where we want to see our science begin to intersect with patient care. This is where applied science may do the most good. This is where new therapies can meet treatment-naïve tumors.

Treatment-naïve tumors are invaluable for research, and the Graham Center is an ideal provider for patient specimens. Traditionally, Wistar received most tumor samples from academic medical centers, which are often seen as the option of last resort for patients who have failed previous rounds of therapy or whose disease has advanced and spread.

Tumor specimens collected for study at these centers are genetically distinct from treatmentnaïve tumors, as they have “evolved” to survive treatment or to spread through the body. At Wistar, we see this time and again in different diseases. A treatment-naïve melanoma tumor, for example, is practically unrecognizable, genetically speaking, when compared with advanced-disease tumors. In fact, the scientists of Wistar’s Melanoma Research Center have published extensively on how new therapeutics, such as BRAF inhibitors, exert an evolutionary pressure on melanoma tumors.

The vast majority of new drugs are developed from studying advanced tumors and most drug trials occur on patients with advanced disease. By testing new therapies against treatment-naïve tumors, we can obtain a better idea of how drugs might perform at community hospitals—the front line of the fight against cancer—and thus provide clinicians with a much better means of predicting how their patients might do on a given therapy.

Practical Aspects of Partnership

This partnership has brought cutting-edge cancer research to these patients in the community, while also providing outstanding opportunities for collaboration with our clinical colleagues that will inform our laboratory work and ultimately lead to better therapies.

Indeed, Wistar could find no better partner in the region with which to collaborate to conduct clinical trials. At 24%, the Graham Cancer Center has one of the nation’s highest patient accrual rates into NCI clinical trials, far above the national average of 3%.

Of course, for such a partnership to work in practice, staffs on both sides must become part of the process. Early on in the collaboration, we built substance into this partnership by appointing Graham Cancer Center’s medical director, Nicholas J. Petrelli, MD, to become Wistar’s associate director for Translational Research. With Petrelli on hand to provide practical advice, honed from years of experience, Wistar’s scientists have begun to tailor their research programs with translational medicine firmly in mind—not just as lip service to grant applications.

In my own research, I see firsthand the potential of our collaboration with a community cancer center. My laboratory recently demonstrated the potential of an inhibitor currently in development, which we call gamitrinib, to effectively attack tumor mitochondria, sensitizing tumor cells to other targeted therapies. We have spent the last decade honing and refining the effectiveness of this inhibitor, and we have recently received funding from the US Department of Defense to conduct the final tests and chemical studies that will allow us to file an Investigational New Drug application for gamitrinib as a prostate cancer therapy.

When it comes time for a clinical trial, you can be certain that the first person I call will be Dr Petrelli.