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New CDK4/ARK5 inhibitor against multiple myeloma (second most prevalent blood cancer)

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CDK4/ARK5 inhibitor has been identified as a potential drug candidate for the second most prevalent blood cancer- multiple myeloma which is a fatal plasma cell neoplasm and against which most of the existing therapies have gradually developed drug resistance. The pioneer study was conducted by the Mount Sinai’s Icahn School of Medicine. 

Each year, 16,000 Indians are diagnosed with this disease and 22,000 new incidences occur in United States.

Mount Sinai team in collaboration with Onconova Therapeutics developed the inhibitor ON123300 which could potentially inhibit CDK4 and ARK5.

ON123300_myeloma      

According to the study published in cancer research ON123300 efficiently caused the tumor cell death as well as stopped the growth of cancer cell in vitro and in vivo mouse models.

Deepak Perumal, main author of the study and postdoctoral scientist at Mount Sinai’s Icahn School briefed that in the myeloma patients the protein MYC is overexpressed therefore in their study they wanted to correlate the inhibition of enzymes CDK4 and ARK5 with the MYC-driven cell proliferation. The team was overwhelmed to see that ON123300 affected only the myeloma cell lines and samples taken from patients with recurring myeloma and caused no side effects on normal peripheral blood cells which actively demonstrated the potency of the compound against multiple myeloma.

cdk4_ark5_mechanism_cancer                                               Downstream signaling events of ARK5

As of 2009 more than 10 CDK inhibitor candidates have either gone through or are currently in clinical trials. Palbociclib-CDK4 and CDK6 inhibitor showed good results in phase II clinical trial for estrogen-positive, HER2-negative advanced breast cancer.

Dr. Samir Parekh, co-author of the study and  associate professor of medicine, haematology and medical oncology at the Icahn School mentioned that, it was the only study that illustrated the potential cytotoxicity of CDK4/ARK5 inhibition in multiple myeloma. He was hopeful that the study would provide a good foundation for further clinical trials using CDK4/ARK5 inhibitors.

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