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 the journal Cell Reports.

“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, DVM, DSc, 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, MD, 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.”