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Wistar Science Highlights: Melanoma Gene, Breast Cancer and African American Women, Anti-Tumor Immunity

Several new scientific studies by Wistar researchers covering a variety of different cancers and how they might be better identified or treated were recently published. Here are some brief recaps of what our Wistar scientists found.

“Sweet Spot” in Tissue Stiffness Promotes Cancer’s Spread

Cancer becomes more difficult to treat once it spreads from one organ to others throughout the body. In order for cancer cells to do this, they must break away from a tumor and pass through a protective “netting” called the extracellular matrix.

Ashani Weeraratna, Ph.D., Ira Brind Associate Professor and program leader of the Tumor Microenvironment and Metastasis Program at Wistar, and her lab, collaborated with Vivek Shenoy, Ph.D., professor in the Department of Materials Science and Engineering in Penn’s School of Engineering and Applied Science, to study what causes this to happen.

They were able to show that cancerous cells communicate with this “netting” and then elongate into torpedo-like shapes in order to break through and spread to other organs. The team from Penn used computer simulations to create the effect, which Wistar scientists then confirmed in melanoma cells.

“This study reaffirms, from a mechanobiology standpoint, the crucial role of tumor microenvironment in orchestrating the fate of cancer cells and dictating prognosis and response to therapy,” Weeraratna said.

Is an Anti-Aging Gene a Valuable Therapeutic Target for Melanoma?

In another study from the Weeraratna lab, researchers showed how a drug used to treat diabetes may be able to inhibit the growth of melanoma in older patients.

Melanoma is linked more closely to aging than many other types of cancers. The disease, which is the most aggressive form of skin cancer, is also very difficult to treat, with many patients relapsing after being treated with chemotherapy or targeted therapy.

In an animal model, they demonstrated that the diabetes drug promoted increased levels of an anti-aging protein called Klotho. When levels of Klotho were higher, they reduced the levels of a protein called Wnt5A that promotes advanced progression of melanoma and therapy resistance. If the effectiveness of this method is confirmed in future studies, this anti-diabetes drug may be used in conjunction with existing therapies to better treat older melanoma patients.

Newly Designed Vaccine Could Improve Anti-Tumor Immunity

The lab of David B. Weiner, Ph.D., Executive Vice President and Director of the Vaccine Center at The Wistar Institute and the W.W. Smith Charitable Trust Professor in Cancer Research, specializes in vaccines with specially designed DNA containing specific instructions for immune cells to recognize and fight against specific antigens – toxins or foreign substances – in order to eliminate them from the body.

Antigens are not just present in viruses but cancer as well, and now the Weiner lab, in association with Inovio Pharmaceuticals, Inc., has developed a vaccine that uses this same technology to fight tumor-associated antigens, or proteins that are expressed by tumor cells but not by normal cells. While this technology has had limited success, a new study showed that targeting Wilm’s tumor gene 1 (WT1), which is overexpressed in many types of cancer, can be targeted by a vaccine that has been designed to make the antigen more recognizable to the immune system.

“Our vaccine also provides an opportunity to combine this approach with another immune therapy approach, checkpoint inhibitors, to maximize possible immune therapy impact on specific cancers,” Weiner said.

Gene Variant Linked to Breast Cancer in Premenopausal African American Women

A gene called TP53 is the most frequently mutated gene in cancer. When operating normally, the p53 protein suppresses tumors, but mutations prevent it from performing this essential function. In addition to mutations, several minor, naturally occurring variants called polymorphisms may increase a risk of cancer.

The lab of Maureen Murphy, Ph.D., professor and program leader of the Molecular and Cellular Oncogenesis Program, collaborated with researchers at Roswell Park Cancer Institute to show that there is a significant association between one of these polymorphisms of the p53 gene and increased risk of developing breast cancer specifically in premenopausal African American women.

“This genetic variant is present exclusively in people of African descent, so our study addresses cancer disparities in African American women, a historically underrepresented group in research studies,” Murphy said. The researchers plan to confirm these results in a larger cohort of patients.