New Treatment Model Causes Multiple Myeloma Cell Death

Researchers seek to develop drugs that are less toxic and achieve longer remissions in multiple myeloma patients.

An extremely effective method that causes cell death in multiple myeloma that targets CDK4 and ARK5 proteins was found in a recent study.

Despite advances in therapies for patients with multiple myeloma, the median survival rate is 7 to 8 years and accounts for 10,000 annual deaths in the United States.

“Even in the era of great drug development, there is an urgent need to develop drugs that are less toxic and achieve longer remissions for all patients,” said study co-author Samir Parekh, MD.

Researchers from Icahn School of Medicine at Mount Sinai in collaboration with Onconova Therapeutics developed the compound ON123300, which includes the inhibitors ARK5 and CDK4.

During the study, published in Cancer Research, the effects of ON123300 were evaluated against myeloma cell lines and primary samples from patients with recurring myeloma.

“ARK5 is critical for myeloma survival and this study suggests a novel function for ARK5 in bridging the mTOR and MYC pathways,” said lead study author Deepak Perumal, PhD. “Given that MYC is critically over expressed in myeloma, we sought to determine whether selective inhibition of ARK5 and CDK4 could be an effective way to target MYC-driven proliferation in myeloma.”

The results of the study showed that the myeloma cells had a sensitivity to ON123300, while normal peripheral blood cells did not. The compound resulted in tumor cell death, halting the cancer cell growth in vitro and in vivo mouse models.

“Our study results show that ON123300 induces cell death and negatively regulates key oncogenic pathways in multiple myeloma cells,” Dr. Parekh said. “This is the first report showing potent cytotoxicity of CDK4 and ARK5 inhibition in MM and provides the foundation for further clinical trials using CDK4 and ARK5 inhibitors to improve outcomes for MM patients.”