PHILADELPHIA — Penn Medicine and The Wistar Institute have been awarded a prestigious $12.1 million SPORE grant from the National Cancer Institute.  The five-year Specialized Programs of Research Excellence, or SPORE, grant will fund four new melanoma research projects that aim to translate fundamental laboratory discoveries into new therapeutics to treat melanoma and other skin cancers.

Melanoma is the deadliest form of skin cancer and the fifth deadliest form of cancer, overall. According to NCI statistics, an estimated 76,100 new cases of melanoma will occur in 2014 in the U.S. alone, and it will kill 9,710 people. If caught early, melanoma is considered treatable; however, therapies showing lasting effects for late-stage, metastatic melanomas are greatly needed.

Meenhard Herlyn, DVM, DSc, the Caspar Wistar Professor in Melanoma Research and director of The Wistar Institute  Melanoma Research Center, will serve as the Principal Investigator, and Lynn M. Schuchter, MD, chief of Hematology/Oncology and leader of the melanoma program at Penn’s Abramson Cancer Center, will serve as Co-Principal Investigator of the grant.

“We’re honored to be recognized by the NCI with this SPORE grant, and thankful it will allow all of us to expand on this collaboration—which has already led to important developments in melanoma,” said Schuchter.  “From targeted therapy to immunotherapy, these melanoma projects—and the people leading them—are at the forefront of medicine, with an ultimate goal of translating basic research from the laboratories into patient care more quickly.” 

Other Penn faculty involved with the project include Carl H. June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine, Robert Vonderheide, MD, DPhil, the Hanna Wise Professor in Cancer Research in the Abramson Cancer Center, Ravi K. Amaravadi, MD, assistant professor of Medicine in the division of Hematology/Oncology in the ACC, and Katherine Nathanson, MD, an associate professor in the division of Translational Medicine and Chief Oncogenomics Physician for the ACC.

The four SPORE melanoma research projects include:

1. Targeted Combination Therapy for Melanoma

Investigators: Herlyn and Schuchter

Targeted therapies—drugs that bind to and inhibit proteins that may cause disease—have shown great promise in melanoma, although patient tumors inevitably develop resistance to these drugs. This study will look at the effects of combining drugs that targets mutant BRAF proteins and drugs that targets the protein PI3K. Both mutant BRAF and PI3K are potent drivers of melanoma tumors, and the researchers believe that targeting both proteins at once may overwhelm the ability of the tumor to develop resistance.

2. Autophagy Modulation for Melanoma Therapy

Investigators: Amaravadi and David Speicher, Ph.D. (Wistar)

This project is designed to test the idea that inhibiting autophagy (cancer cells "eat themselves" in order to survive) will have a synergistic effect when used with BRAF inhibitors.

3. Association of Inherited Variation in Immune Mediated Adverse Events and Response to Ipilimumab

Investigators: Nathanson and Peter Kanetsky, PhD (H. Lee Moffitt Cancer Center & Research Institute)

The goal of this project is to find the genetic markers that predict which patients do poorly when they take Ipilimumab, an FDA-approved drug that targets CTLA4, a protein that can slow the immune response to cancer. While the drug is designed to re-activate a patient's immune system, in some patients it causes an over-reaction that is capable of causing death. By identifying genetic markers in over 1,000 patients from recent clinical trials, the researchers hope to identify which patients may be able to use Ipilimumab safely and effectively.

4. Engineered T Cell Therapy for Melanoma

Investigators: Vonderheide and June

This project explores the use of "adoptive cellular therapy"—modifying a patient's own T cells to target metastatic melanoma cells. The researchers will conduct a clinical trial that will take a patient's T cell and transform them to target c-MET, a protein that cancer cells exhibit in overabundance on their surface.

In addition to the research projects, the SPORE grant will also support three "cores" designed to further support the SPORE team's scientific efforts. These cores include an administrative core to maximize collaboration between Penn and Wistar; a biospecimen and pathology core to provide SPORE researchers with high quality melanoma tumor samples; and a biostatistics core to help analyze and disseminate research results of the SPORE's experiments and clinical studies.

"Melanoma incidence may be on the rise, but I believe we are at the cusp of a revolution in new melanoma therapies and therapeutic strategies, powered by newly emerging research," said Herlyn. "This SPORE benefits from over 30 years of teamwork in melanoma research between The Wistar Institute and the University of Pennsylvania, and we have put into place a collaboration that will certainly reduce the threat of this terrible disease."

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.

The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.

The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is an $11.1 billion enterprise powered by more than 49,000 talented faculty and staff.

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