Team Studies Ways to Treat Melanoma by Examining Roles of Cell Framework

During a membership event April 29, the Cincinnati Cancer Center awarded over $200,000 in pilot grants to members and basic scientists who are collaborating to find out more about various cancers with hopes of generating more data and additional funding.

Two teams received Mentee-Mentor Partnership Awards to encourage CCC members, especially young investigators, in cancer research.

Yuhang Zhang, PhD, associate member of the Cincinnati Cancer Center, assistant professor in the James L. Winkle College of Pharmacy, member of the UC Cancer Institute and principal investigator of the $19,640 CCC pilot grant, is researching ways to treat the deadliest form of skin cancer: melanoma.

After coming to UC from the University of Pennsylvania in 2010, he quickly teamed up with his mentor Zalfa Abdel-Malek, PhD, member of the CCC, professor in the department of dermatology at the UC College of Medicine and member of the UC Cancer Institute, to collaborate on a number of studies examining the molecular pathways that lead to melanoma.

For this research, Zhang is investigating the roles and functions of fibroblast in melanoma stroma (the framework of the cells) in promoting melanoma development by regulating the expression of a protein called beta-catenin.

Fibroblasts drive the growth and migration of melanoma by providing structural support.

"Melanoma is one of the most challenging solid tumors with high rates of mutation and is notorious for its drug resistance and tendency to spread. For years, researchers have concentrated their efforts on the identification of ways to either kill malignant tumor cells or restrict their growth. Unfortunately, poor treatment outcomes have frustrated clinicians due to the genetic instability that frequently occurs in malignant melanoma cells,” Zhang says.

He says the formation of melanoma is driven by not only malignant tumor cells but also by their changed communication with other non-malignant cells, including fibroblasts, endothelial and inflammatory cells, in the tumor stroma.

"Evidence has shown that a larger number of tumor-associated fibroblasts in the tumor stroma is associated with an increased risk of metastasis and a poor prognosis. Therefore, targeting the fibroblast to destroy the microenvironment in which tumor cells live has emerged as a new and promising therapeutic strategy,” he continues.

Zhang says that little is known about how normal skin fibroblasts, a possible source of tumor-associated fibroblasts, become reprogrammed to build an optimal microenvironment for tumors to grow and progress.

"Using animal models, we are looking to alter the tumor microenvironment that is supporting melanoma progression by disabling tumor-associated fibroblasts through the manipulation of beta-catenin signaling,” he says, adding that beta-catenin regulates the coordination of cell adhesion and gene transcription. "The objective of our study is to explore the molecular mechanisms controlling the interactions between these fibroblasts and melanoma cells that foster cancer.

"We hope to gain new insights to eventually develop clinical applications targeting tumor-associated fibroblasts for melanoma treatment.”

Zhang says he feels greatly honored to receive this award and even more pleased to be working on melanoma research with someone as esteemed as Abdel-Malek.

"Dr. Abdel-Malek is not only an exceptional mentor for directing my cancer research but is also an ideal advisor to train and assist me with intellectual collaboration, manuscript writing and grant management during my career development” says Zhang, adding that they have been working closely together and have already submitted a grant application to the National Cancer Institute.

Abdel-Malek says the admiration goes both ways.

"I’m very happy and excited to work with Dr. Zhang,” she says. "He did excellent work as a postdoc, and working together was a no-brainer for us. Mentorship opportunities are so important, and I base this on my experience when I was a junior faculty member, struggling to gain funding. It all comes from experience.

"This funding and the skills it will help develop are invaluable.”

*As a further development, the CCC award may be used to team up with the Melanoma Research Alliance to sponsor Zhang's research.

The University of Cincinnati, Cincinnati Children’s Hospital Medical Center and UC Health have created the Cincinnati Cancer Center—a joint effort designed to leverage the strengths of all three organizations in order to provide the best possible cancer diagnostics, research, treatment, and care for individuals in the Tristate region and the nation. To learn more, visit cincinnaticancercenter.org.