Research suggests strategies for overcoming treatment resistance in prostate cancer

Jan. 20, 2015

Researchers at Roswell Park Cancer Institute (RPCI) have identified two genes that appear to be simultaneously overexpressed in aggressive prostate cancers resistant to the androgen-targeted treatments enzalutamide and abiraterone acetate. Although both genes, Top2a and Ezh2, have previously been linked to aggressive prostate cancer, results of this study marked the first recognition of their simultaneous overexpression. Both play multiple roles—including in gene regulation—within the cell. The findings were recently published in the scientific journal Oncotarget.

“In two independent preclinical studies involving prostate cancer models that closely represent the clinical dilemma of resistance to androgen-targeted treatments, our results suggested a high degree of therapeutic efficacy for this approach,” says Leigh Ellis, PhD, assistant professor of Oncology in the Department of Pharmacology and Therapeutics. “This study deepened our knowledge of the etiology of aggressive prostate cancer and will be the basis of future investigations that we hope will lead to discovery of additional biomarkers and therapeutic targets.”

Informed by these latest findings, Dr. Ellis and his team intend to zero in on the pathways that are deregulated by the two genes. The team has also implicated the simultaneous overexpression of both genes in other types of cancer, suggesting that the biomarkers could be useful in discovering effective therapies for many disease sites.

Dr. Ellis hopes the results of the preclinical trials will lay the groundwork for a clinical trial for prostate cancer patients whose disease is resistant to enzalutamide and/or abiraterone acetate.

Read the study abstract on the Oncotarget website