Mount Sinai: CDK4/ARK5 inhibitor could offer new treatment for multiple myeloma

Mount Sinai's Samir Parekh

Pfizer's ($PFE) CDK4/6 inhibitor Ibrance made a splash last year when it won a speedy FDA nod for breast cancer, with competitors from Novartis ($NVS) and Eli Lilly ($LLY) in pursuit. But related drugs may also have applications beyond breast cancer: researchers from Mount Sinai's Icahn School of Medicine have identified a CDK4/ARK5 inhibitor as a potential new weapon against multiple myeloma, a fatal blood cancer.

While there is a host of drugs and treatment options to manage multiple myeloma, the cancer is still incurable. Patients eventually develop drug resistance and more than 10,000 Americans die from multiple myeloma each year.

Working with Onconova Therapeutics, the Mount Sinai team developed a compound that would inhibit CDK4 and ARK5. In a study published in Cancer Research, they found that the inhibitor, ON123300, caused tumor cell death and halted cancer cell growth in vitro and in vivo mouse models.

Because the protein MYC is overexpressed in myeloma, the Mount Sinai team wanted to see if inhibiting the enzymes CDK4 and ARK5 would be an effective way to tamp down MYC-driven cell proliferation in myeloma, said Deepak Perumal, lead author of the study and a postdoctoral scientist at Mount Sinai's Icahn School.

The team found that myeloma cell lines and samples taken from patients with recurring myeloma responded to ON123300, but normal peripheral blood cells were unaffected, which confirmed the potent anticancer effect of the compound.

This is the first study that demonstrates potent cytotoxicity of CDK4/ARK5 inhibition in multiple myeloma, said Dr. Samir Parekh, a co-author of the study and associate professor of medicine, hematology and medical oncology at the Icahn School, in the statement. "[It] provides the foundation for further clinical trials using CDK4/ARK5 inhibitors to improve outcomes for [multiple myeloma] patients," he said.

In addition to their applications in breast cancer, CDK inhibitors have also shown promise in pancreatic cancer. UT Southwestern researchers found that CDK4/6 inhibitors altered the metabolism of pancreatic cancer cells, suggesting that they could be paired with another drug that exploited the metabolic change.

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