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Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in men in the United States, according to the National Cancer Institute (NCI).

It grows slowly and has a positive prognosis if detected early; however, prostate cancer typically spreads to the bone when it does grow, and there are currently no curative treatment options for advanced disease.

VCU Massey Cancer Center researchers Paul B. Fisher, M.Ph., Ph.D., FNAI, and Xiang-Yang (Shawn) Wang, Ph.D., were recently awarded $2.3 million in total funding through a five-year R01 grant from the NCI to understand the genetic processes that contribute to prostate cancer growth and to develop novel therapeutic strategies to effectively treat late-stage disease.

“Current therapeutic approaches have generally proven ineffective in treating patients with advanced prostate cancer that has metastasized to the bone,” said Fisher, who is a member of the Cancer Biology research program and the Thelma Newmeyer Corman Endowed Chair in Oncology Research at Massey, director of the VCU Institute of Molecular Medicine (VIMM) and chair of and professor in the Department of Human and Molecular Genetics at the VCU School of Medicine.

Fisher added, “Understanding the mechanisms contributing to prostate cancer progression — including those involving the tumor cell and its microenvironment — and developing improved therapeutic strategies to eradicate bone metastases are crucial for reducing prostate cancer complications and death.”

Through previous research, Fisher and Wang have established that the gene MDA-9 promotes cancer invasion and growth. Using newly developed preclinical models of prostate cancer bone metastases, they will use the grant funding to study how MDA-9 supports the spread of tumor cells from the prostate to the bone and evaluate the efficacy of a drug called PDZ1i to block the function of MDA-9 and target prostate cancer cells in and directly around the bone.

Fisher and Wang also previously discovered that T cells — immune cells that help fight cancer — can be armed with the gene MDA-7/IL-24 to broadly attack solid tumors and survive better in the tumor microenvironment. Using this technology, they will engineer T cells with MDA-7/IL-24 and investigate their capacity to more effectively target and kill prostate cancer bone metastases.

Because PDZ1i can reprogram the immune system’s response to cancer, Fisher and Wang will also investigate the combined ability of super-engineered T cells producing next-generation MDA-7/IL-24 and MDA-9-targeted drugs to seek out and eliminate tumor cells.

“Using clinically effective immunotherapy in combination with molecular-targeted therapies may provide a safe and effective treatment option for advanced prostate cancer that has spread to the bone,” said Wang, who is co-leader of the Developmental Therapeutics research program and holds the Harry and Judy Wason Distinguished Professorship at Massey, is a professor of human and molecular genetics at the VCU School of Medicine and is the associate director of immunology in the VIMM. “We anticipate our findings will offer a more precise molecular understanding of bone metastasis development, enable us to design improved cellular immunotherapies and allow us to rapidly translate these technologies and strategies into the clinic for maximum therapeutic potential.”

Written by: Blake Belden