DNA Methylation Inhibitor Therapy for Testicular Germ Cell Tumors

Background

Testicular cancer is the most common cancer among teenagers and young men between the ages of 15 and 35. Approximately 80% of patients can be cured with current therapies. However these therapies have not changed greatly since the mid-1980s and are very toxic. This results in substantial long-term side effects that greatly impact quality of life for many decades. In addition, 15-20% of patients cannot be cured even with the cytotoxic drugs and die.

Project Goal

This project is based on our novel findings that testicular cancer cells are especially susceptible to a new form of therapy called epigenetic therapy that targets DNA methylation. We showed that this is because of a unique molecular feature of testicular cancer. We found that testicular cancer cells can be killed with doses of DNA methylation inhibitors 1000-fold lower than doses needed to kill other types of cancers. This new therapy also kills testicular cancer cells that are resistant to the cytotoxic drugs. We hypothesize that low dose DNA methylation inhibitor therapy will be able to treat testicular cancer patients who would otherwise die from their disease and also provide a less toxic therapy to all patients. This application is designed to lay the framework to move these basic science findings to the clinic. This will be done through a partnership between basic science researchers at Dartmouth and oncologists at Indiana, one of the major testicular cancer centers in the US that care for patients that have failed available therapy.