Targeting Dysregulated Histone-Modifying Enzymes Driving Prostate Cancer Cell Survival After Androgen Deprivation Therapy
Abstract
An underappreciated area of prostate cancer management is the persistent cancer cells that remain after treatment with androgen-deprivation therapy (i.e., hormone removal) for advanced prostate cancer. Eradication of these persistent prostate cancer cells is critical to improve treatment outcomes. Our research has demonstrated that these persistent cells after androgen removal upregulate specific genes that help with survival and growth. One major regulator of cell behavior involves a series of enzymes called histone modifiers. We have discovered that unique histone patterns result in androgen-resistant cells that are controlled by these enzymes. In this proposal, we will examine the hypothesis that these enzymes represent a potential Achilles heel that plays a key role in the resistance response of prostate cancer cells to the combination of hormone removal and histone modifier inhibitors. Specifically, we will test this novel approach in cell culture models and clinically relevant human prostate cancers. Our studies could lead to a new treatment paradigm for prostate cancer to eradicate persistent cells after hormone removal that has the potential to dramatically improve treatment outcomes. This study addresses the development of cancer resistance in prostate cancer patients, and furthermore should be readily translated into the clinic since many histone modifiers inhibitors are already and androgen-deprivation therapy is currently in use.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310127
Entities
People
- David F Jarrard
Organizations
- United States Army
- University of Wisconsin–Madison