A class of drugs known as CDK4/6 inhibitors, which have been approved for treating some types of breast cancer, may have much more to offer than previously thought. Not only can they stop tumors from growing by halting cell division, but they can also “spur the immune system to attack and shrink” them.
This was the main finding of a new study from the Dana-Farber Cancer Institute and Brigham and Women’s Hospital, both in Boston, MA, the results of which have been published in the journal Nature.
CDK4/6 inhibitors are a class of drugs that work by blocking certain proteins called cyclin-dependent kinases (CDKs) 4 and 6, which promote the growth of cancer cells.
At present, these drugs have only been approved for treating some patients with metastatic breast cancer, “but they’ve also shown promise against others types of tumors in clinical trials,” says co-first author Shom Goel, Ph.D., of the Dana-Farber Cancer Institute.
In the United States, around 1 in 8 women will develop invasive breast cancer during their lifetime. Men can also get breast cancer, although their lifetime risk is much smaller, at approximately 1 in 1,000.
Dr. Goel says that in early clinical trials of CDK4/6 inhibitors in breast cancer patients, they noticed that not only did the tumors stop growing – as you might expect with drugs that arrest cell division – but they also shrank, “sometimes quite dramatically.”
He and his colleagues believe that scientists are only just beginning to discover the full potential of what CDK4/6 inhibitors may have to offer.
In their study, the researchers found that not only did the drugs stop cancer cells dividing, but they also promoted anti-cancer immunity in two ways.
One way was by getting cancer cells to increase their display of abnormal proteins on their surfaces, which made it easier for the immune system to find and destroy them.
Another way that the CDK4/6 inhibitors helped the immune system to attack tumors was by reducing immune cells called T regulatory cells (Tregs). Tregs usually dampen immune response, so the fewer there are, the fiercer the attack.
The team discovered the tumor-halting and tumor-shrinking effects when they treated mice with breast cancer and other solid tumors with the CDK4/6 inhibitor abemaciclib. The experimental drug recently received priority status from the U.S. Food and Drug Administration (FDA).
When they analyzed biopsy samples from women taking part in a clinical trial testing a CDK4/6 inhibitor for breast cancer, the researchers observed the same effects that they saw in the mice; not only did the drug halt the tumor cell cycle, but it also spurred the immune system to attack the tumors.
The authors explain that clinical trials show that around 20 percent of breast cancer patients treated just with abemaciclib show a “significant response,” while another 20 to 30 percent experience “stabilizations of tumor growth.” These effects emerge within 4 months of starting on the drug.
Dr. Goel and colleagues also found that the anti-cancer effect was even stronger when they coupled the CDK4/6 inhibitors with other immunotherapy drugs known as checkpoint inhibitors, which can stop cancer cells evading the immune system.
“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.”
The team says that more work should be done to discover why CDK4/6 inhibitors appear to benefit some patients more than others. They also hope that their findings will encourage others to look at how to combine CDK4/6 inhibitors with different immunotherapies.