Researchers have discovered what may be a promising new approach for controlling aggressive, treatment-resistant forms of prostate cancer. Leigh Ellis, PhD, and colleagues 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.
“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 Dr. Ellis, 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.
The paper, “Top2a identifies and provides epigenetic rationale for novel combination therapeutic strategies for aggressive prostate cancer,” is available online in Oncotarget. The study used shared resources supported by RPCI’s Cancer Center Support Grant from the National Cancer Institute (P30CA016056).
Top2a identifies and provides epigenetic rationale for novel combination therapeutic strategies for aggressive prostate cancer, Jason S. Kirk, Kevin Schaarschuch, Zafardjan Dalimov, Elena Lasorsa, ShengYu Ku, Swathi Ramakrishnan, Qiang Hu, Gissou Azabdaftari, Jianmin Wang, Roberto Pili and Leigh Ellis, Oncotarget, published 26 December 2014.