Scientists Generate a Comprehensive Collection of Pre-clinical Models for Melanoma Research

Scientists Generate a Comprehensive Collection of Pre-clinical Models for Melanoma Research

November 14, 2017

PHILADELPHIA — (Nov. 14, 2017) — Researchers at the The Wistar Institute have created a comprehensive collection of patient-derived xenografts (PDXs) for pre-clinical modeling of melanoma that can be used to develop personalized treatments and evaluate responses to different types of therapy. An exhaustive genetic and genomic characterization of this collection was performed by a collaborating team from the Perelman School of Medicine at the University of Pennsylvania, and was presented in a separate study. These findings were published as companion papers in Cell Reports.

Advanced melanoma is a deadly disease, but in the past decade several new therapeutic options have become available to patients through advances in immunotherapy and precision medicine.

“In order to keep up with the development of new treatment strategies, we need improved models that reflect the complex landscape of melanoma,” said Meenhard Herlyn, D.V.M., D.Sc., Caspar Wistar Professor in Melanoma Research and director of The Wistar Institute Melanoma Research Center and lead researcher on one of the studies. “We created a live tissue resource that represents the full spectrum of clinical, therapeutic, mutational and biological heterogeneity of the disease and will be a valuable tool available to the melanoma research community.”

PDXs are cancer models created by transplanting a patient’s primary tumor directly into an immunodeficient mouse. Therefore, PDXs provide a source of tumor tissue that closely resembles the clinical lesion and grows in an environment that mimics the patient’s primary tumor site better than a petri dish. Several studies have shown that PDX models maintain the genetic and epigenetic alterations found in the patient and exhibit similar responses to antitumor drugs, confirming the potential of PDX models in melanoma.

Herlyn and colleagues established 319 PDXs and 140 frozen live tissues from 384 melanoma patients, mirroring the clinical diversity of the disease for age, stage, type of melanoma and sites where the cancer has metastasized. The collection also included tumors with rare mutations and patient-matched PDXs deriving from tissues collected before and after therapy. Because of its large scope and heterogeneity, this collection may be suitable for early stage clinical trials and drug discovery studies, significantly reducing the costs compared with human trials.

The Herlyn team used the newly established PDX models for small-scale studies of drug screening, validation and response to therapy, providing a proof of concept for the use of the PDX collection.

Wistar investigators worked very closely with the team at Penn Medicine lead by Katherine L. Nathanson, M.D., the deputy director of the Abramson Cancer Center, who performed genetic and genomic analyses of the PDX, cell lines, and patient samples.

“In order to establish useful models for future studies, knowing which genetic and genomic changes drive the cancers is essential,” Nathanson said. “We found all melanoma types previously defined in large scale sequencing projects, and were able to better define rare genetically defined sub-types due to our large sample set.”

Nathanson also said this study demonstrates the value of collaborative research to utilize the expertise of people in multiple disciplines.

Work for the two studies was supported by National Institutes of Health grants P01 CA114046, P01 CA025874, R01 CA047159, P50 CA174523-02 SPORE on Skin Cancer, R01 CA182635, R01CA198015, 5P30 CA016520. Additional funds were provided by the Melanoma Research Alliance, the Margaretta and R.R.M Carpenter, Sr Cancer Stem Cell Research Program, the University of North Carolina Cancer Research Fund, philanthropic contributions to The University of Texas MD Anderson Cancer Center Melanoma Moon Shot Program, and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. Core support was provided by the Cancer Center Support Grants P30 CA010815, P30 CA016672 and the Melanoma SPORE P50 CA093459.


Media Contacts:

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The Wistar Institute                                                                                         Penn Medicine

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About The Wistar Institute

The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible.

About Penn Medicine/Perelman School of Medicine

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.