Demonstrate Synergetic Anti-tumor Effects of AR-42 with Cisplatin in Bladder Cancer Models
Arno Therapeutics, Inc. (OTCQB: ARNI), a clinical stage biopharmaceutical company primarily focused on the development of oncology therapeutics, today announced that data from a preclinical study demonstrate its histone-deacetylase (HDAC) inhibitor AR-42 in combination with cisplatin has a synergistic anti-tumor effect in bladder cancer models. These data were recently published online ahead of print in The Journal of Urology.
AR-42 is a novel oral, broad-spectrum agent therapy currently in early clinical development. As a deacetylase inhibitor of both histone and non-histone proteins, AR-42 has demonstrated greater potency and activity in solid tumors and hematological malignancies when compared in preclinical studies to vorinostat (also known as “SAHA” and marketed as Zolinza® by Merck), the first of four marketed compounds in the class. AR-42 may possess additional histone-independent mechanisms, which may contribute to its superior profile in vitro and in vivo.
The study, led by Arnold I. Chin, MD, PhD, Assistant Professor, Department of Urology at University of California, Los Angeles (UCLA) Jonsson Comprehensive Cancer Center (JCCC), demonstrates the ability of AR-42 to synergize with cisplatin to augment the destruction of bladder cancer cells in vitro and in vivo, and to preferentially target the bladder cancer stem cell population. Specifically, the research shows that the combination of AR-42 and cisplatin synergistically kills bladder cancer cells through apoptosis and influences tumor growth and differentiation in vivo. This synergistic effect may also improve the efficacy and overall response rate of cisplatin, and allow for a lower dosage, resulting in potentially lower toxicities in patients. Furthermore, when tested on specific bladder cancer stem cell populations (marked by surface markers CD44+ and CD49f+), AR-42 showed greater efficacy, with and without cisplatin.
Alex Zukiwski, MD, Chief Executive Officer of Arno Therapeutics, commented:
These results are encouraging and, although early, establish preclinical evidence that AR-42 may have potential in conjunction with cisplatin-based chemotherapy in the treatment of bladder cancer. Overall, the findings support further clinical investigation of AR-42 in this indication. We are grateful to lead author Dr. Arnold Chin and his team at UCLA for their research and look forward to additional collaboration as we continue to explore this novel therapy.
Bladder cancer affects more than 54,000 men and 17,000 women in the United States annually, making it the fourth most common cancer among men and ninth most common cancer in women. Bladder cancer treatments have remained unchanged for decades and continue to be mainly composed of cisplatin-based chemotherapy regimens that have limited response rates and efficacy. Research has shown that molecular analysis of bladder cancer reveals a high incidence of mutations in chromatin regulatory genes, suggesting a therapeutic avenue for HDAC inhibitors.