Targeting the Polycomb Pathway for Testicular Cancer Therapy in Adolescents and Young Adults
Abstract
Topic Area: Pediatric, adolescent, and young adult cancers; Military Health Focus: Mission Readiness; Gaps in treatment, quality of life/survivorship Testicular cancer is an aggressive disease that inflicts men in the prime of life, and it is the most common cancer in males aged 15-35 years. While the majority of testicular cancer patients can be cured with the old cytotoxic drugs, especially a drug called cisplatin, a significant portion of patients fail this therapy and die from their disease. These cytotoxic therapies are harsh and nonspecific and cause substantial life-long side effects and quality of life issues. For other cancers like breast, lung, melanoma, etc., new, less toxic “targeted” and immune therapies have revolutionized patient care. However, this is not the case with testicular cancer, which is still treated with the same cytotoxic drugs introduced in the 1970s. There are reasons to believe, and we contend, that testicular cancer may be especially sensitive to a new form of therapy called epigenetic therapy, even for those patients that are resistant to the old cytotoxic therapies. However, since this area is so new, there is very little known about which specific epigenetic drugs might work in testicular cancer. Our work discovered a specific epigenetic drug that works very well to reverse the cisplatin resistance that occurs in a significant number of testicular cancer patients. This is a form of targeted therapy. The goal of the project is to further validate this epigenetic therapy in cell and animal models and to perform experiments that will provide markers of whether a patient’s tumor will respond or is responding to the therapy. As the specific epigenetic drug we are interested in has already been tested in animals, this work could rapidly be advanced to the clinic. We have already shown proof of concept that a different epigenetic drug, something called a DNA methylation inhibitor, can be used to treat cisplatin-resistant disease in a testicular cancer clinical trial. So, while other targeted therapy approaches have failed in testicular cancer, we contend – and our work supports – that epigenetic therapy may be the means to move testicular cancer therapy out of the stone age and into a more modern and hopefully, less toxic future. We envision combination epigenetic therapy could be used alone or as a means to lower the amount of the old cytotoxic therapy needed to treat testicular cancer patients and as a means to rescue those testicular cancer patients that no longer even respond to the old cytotoxic drugs. Further, a greater understanding of the hypersensitivity and curability of testicular cancer has the potential to inform strategies to sensitize other solid tumors to conventional chemotherapies. The U.S. Military has one of the most concentrated populations of men in the TGCT age group, and military health systems are diagnosing and treating a larger number of testicular cancer patients compared with civilian health centers. Hence testicular cancer clearly has a significant impact on U.S. Servicemen, their families, and the military health system both in terms of quality of life and health care costs encumbered by military health care providers.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110903
Entities
People
- Michael Spinella
Organizations
- United States Army
- University of Illinois Urbana–Champaign