Men with penile squamous cell cancer could benefit from a combined approach to their cancer therapy, because targeted chemotherapy or immunotherapy alone – which may work for other kinds of cancers – is not effective for this cancer, according to a study by University of Notre Dame researchers and collaborators.
The study was completed in part in the laboratory of lead researcher Xin Lu, the John M. and Mary Jo Boler Assistant Professor in the Department of Biological Sciences and junior chair of the Boler-Parseghian Center for Rare and Neglected Diseases. The study, published in Nature Communications, evaluated the use of an FDA-approved drug for thyroid and kidney cancers, then immunotherapy, and finally a combination of the two in a genetically engineered mouse model.
Though both therapies worked marginally on their own, the combination led to a destruction of the penile tumor because they simultaneously reduced two types of immunosuppressive cells. These are the myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs) that act together to suppress the body's immune response. A reduction in both kinds is needed for tumor-killing T cells to eliminate penile squamous cancer cells.
Though penile cancer is rare in in the United States with fewer than 1 man in 100,000 diagnosed each year, it is more widespread in the territory of Puerto Rico, as well as in some parts of Asia, Africa, and South America, Lu said. About half the cases are caused by human papillomavirus (HPV).
“This paper serves as a good resource for this cancer type in general,” said Lu, who is affiliated with the Mike and Josie Harper Cancer Research Institute.
As they performed the research, the team created two genetic models, one with a less aggressive cancer that had a greater chance of responding to chemotherapy alone, and one with a more aggressive type. The mouse models with the more aggressive cancer had less of a chance of responding to the chemotherapy medication, cisplatin. The paper also outlined how the team performed targeted drug screening for treating penile cancer, and compared the immune cells of men with penile cancer with those in the mouse models, demonstrating that they were consistent.
This suggests the combination treatment should potentially translate well in humans, Lu said.
“Another highlight of this type of research for rare cancers is it’s challenging to run clinical trials, since there are simply not enough patients,” Lu said. “Now we have this animal model to mimic human tumors, and it may help pinpoint aspects of the disease.
“Common cancers have a lot of models, but rare cancers are largely neglected,” he said.
In addition to Lu, the other lead researchers are affiliated with the University of Texas MD Anderson Cancer Center and the University of Puerto Rico Comprehensive Cancer Care Center. They have already started on a study into HPV’s role in penile squamous cell carcinoma and hope to usher in a clinical trial.
“There are some early clinical trials on the immunotherapy of penile cancer, but penile cancer is typically lumped in with other rare cancers, an issue that might be better addressed if more international collaborations can be initiated.” Lu said. “I want to thank Kasturi Haldar, (the Rev. Julius A. Nieuwland, C.S.C Professor in the Department of Biological Sciences and Parsons-Quinn Director of the Boler-Parseghian Center for Rare and Neglected Diseases), who provided a lot of support for this research.”
In addition to Lu and his postdoctoral researchers Tianhe Huang at Notre Dame, and those at MD Anderson and the University of Puerto Rico Comprehensive Cancer Care Center, San Juan, other collaborators include researchers from Indiana University Melvin and Bren Simon Cancer Center, the University of Cincinnati, and The University of Texas Health Science Center at Houston McGovern Medical School.
In the United States, the research was supported by the National Cancer Institute of the National Institutes of Health, the Susan G. Komen Foundation, Indiana CTSI, and the Boler Family Foundation Endowment.