Certain drugs have proven to be successful at halting the growth of breast cancer tumors by stopping cell division. But findings from a new study show that these drugs may even be better than initially thought. The research shows that these drugs not only block the growth of tumors, but they also seem to spur the patient’s immune system to attack and shrink the tumors.
The Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, Massachusetts conducted the study in tandem, and its results were published in the journal Nature.
What are CDK4/6 inhibitors?
The class of drugs known as CDK4/6 inhibitors has been approved for treating some forms of breast cancer. These drugs work by blocking certain proteins called cyclin-dependent kinases (CDKs) 4 and 6, which promote the growth of cancer cells. The drugs stop the cancer cells from dividing.
Not just stopping growth
The study by the two Boston research institutions looked at the effects the CDK4/6 inhibitor abemaciclib had on cancer cells, both in mice and in human clinical trials. The study was co-authored by Shom Goel, Ph.D., of the Dana-Farber Cancer Institute, who said the data show that the tumors did stop growing once the CDK4/6 drugs were administered, as would be expected. But that’s where it got interesting because not only did the tumors stop growing, but they also began to shrink. The study notes that the shrinkage was “sometimes quite dramatic.”
How are these drugs doing this?
The study found that these drugs used two methods to get the body to attack these tumor cells.
First, the drugs made the cancer cells increase the display of abnormal proteins on their surfaces. These displays made it easier for the immune systems to find and destroy the cells, shrinking the tumor.
The second method the CDK4/6 drugs used to boost the immune response was to reduce immune cells called T regulatory cells (Tregs). Tregs are the chaperones of the immune response, dampening the level immune response. When there are fewer Tregs, the immune system attacks the tumor cells much more actively.
Not just in mice
The study confirmed the results they saw in mice when they analyzed biopsy samples from women involved in a clinical trial of abemaciclib. In the human samples, the drug halted tumor growth, and it spurred an active immune response to attack and shrink the tumors.
The study cited these statistics. Twenty percent of breast cancer patients treated with abemaciclib showed a “significant response.” Another 20 to 30 percent experienced “stabilizations of tumor growth.” The study said these effects were evident within just four months of the patients starting the drug.
In the study, Dr. Goel also wrote that the immune attack response became even stronger when the CDL4/6 inhibitor was coupled with other immunotherapy drugs known as “checkpoint inhibitors,” whose job is to stop cancer cells from 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 study states.
The study recommends further study to try and understand why CDK4/6 inhibitors benefit some patients more than others. It also says that more research is needed to understand how to boost immune response when CDK4/6 inhibitors are combined with different immunotherapies.