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AACR 2023: Novel Targeted Combination Therapy for Metastatic Castration-Resistant Prostate Cancer

By: Emily Rhode
Posted: Friday, April 21, 2023

DNA repair defects are present in 20% of patients with metastatic castration-resistant prostate cancer. The selective ATR kinase inhibitor ceralasertib (formerly known as AZD6738) prevents DNA repair and has shown moderate antitumor activity as a monotherapy in prostate cancer treatment; however, limited efficacy has been shown in patients with metastatic castration-resistant prostate cancer. A new study presented by Wafik S. El-Deiry, MD, PhD, FACP, of Brown University, Providence, Rhode Island, and colleagues during the American Association for Cancer Research (AACR) Annual Meeting 2023 (Abstract 1070/14) reported the combination therapy of ceralasertib and the oral Akt/ERK inhibitor TIC10/ONC201 may prove to be more effective than ceralasertib alone in the treatment of this type of prostate cancer.

Metastatic castration-resistant prostate cancer tumor cells were treated with the combination therapy of ceralasertib plus ONC20. After 72 hours, researchers used a luminescent cell viability assay to determine the number of viable cells left in culture in a 96-well plate. The preliminary results of the combination therapy showed the two kinase inhibitors worked synergistically, although a mechanism for this effect has yet to be identified. The authors hope to build upon these results with data from ongoing studies using Western blotting and cytokine profiling to determine the synergistic mechanism behind the combination therapy.

“Our results aim to solve the overarching need in developing novel therapeutic strategies to overcome resistance in current prostate cancer treatments,” the authors concluded.

Disclosure: For full disclosures of the study authors, visit

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