A relatively recent class of cancer drugs may be more potent than scientists thought, having both the capacity to stop cancer cell division and shrink the tumor.
The drugs belong to a class of their own, called cyclin-dependent kinase (CDK) inhibitors. CDK inhibitors work by blocking the kinase enzymes, namely CDK 4 and CDK 6. Many cancers have high CDK activity, which promotes the unregulated proliferation of cancer cells.
In particular, CDK inhibitors have gained recent attention for being effective against hormone receptor-positive (HR+) breast cancers. Moreover, the CDK inhibitors were found to have limited major side effects in patients, an exceedingly rare feat when it comes to chemotherapies. Just this year alone, the FDA approved two CDK inhibitors for breast cancer in quick succession: palbociclib (Ibrance) in February 2015, and ribociclib (Kisqali) in March 2017. A third drug in this class, abemaciclib, is currently tested in a Phase 3 trial.
But the story with CDK inhibitors is far from over. Researchers from the Dana-Farber Cancer Institute observed that in many instances, in addition to slowed cell division, tumors treated with CDK inhibitors also shrank “quite dramatically.”
The research team systematically studied the effects of CDK 4/6 inhibitors in mouse models of breast cancer. They found that these drugs induced cell cycle arrest, as expected. But the team found CDK 4/6 inhibitors also promoted anti-tumor immunity in two ways. First, the drug forced the expression of key proteins on the cancer cell surface, making them more easily recognizable to the immune system. Second, the drug reduced immune cells known as T regulatory cells (Tregs), which would normally hold back an immune-mediated attack on cancer. The reduction of these cells allow the immune system to attack with more intensity.
Indeed, mice treated with the CDK 4/6 inhibitor showed marked reduction in tumor size. The same phenomenon was later observed in human breast tumor samples. In clinical trials, treatment with abemaciclib, an experimental CDK 4/6 inhibitor, resulted in “significant response” in 20 percent of breast cancer patients. Another 20 to 30 percent showed “stabilization of tumor growth” after four months of treatment.
The researchers also found that CDK 4/6 inhibitors could enhance the potency of other immunotherapy drugs, namely checkpoint inhibitors. "It appears that the CDK4/6 inhibitors might be able to sensitize some patients' cancers to the anti-tumor effects of immune checkpoint inhibitors. The result might be especially encouraging for breast cancer patients, who have derived little benefit from immunotherapy in trials conducted to date,” said Dr. Shom Goel, the study’s co-first author.
“Our findings indicate that CDK4/6 inhibitors increase tumour immunogenicity and provide a rationale for new combination regimens comprising CDK4/6 inhibitors and immunotherapies as anti-cancer treatment,” the team concluded.
Additional sources: MNT
