Blocking a kinase known as CDK7 triggers a reaction that causes the death of prostate cancer cells that have spread and are resistant to standard therapy, according to a new study by researchers at the University of Pennsylvania Abramson Cancer Center, published in Cancer Discovery.
The team identified the role of CDK7 as the on / off switch that controls Med-1, a process that works in association with the androgen receptor to boost prostate cancer growth. Researchers have shown that turning off the switch leads to the death of cancer cells.
Androgen deprivation therapy is a standard approach to treating prostate cancer, but in the course of treatment, most patients will eventually become resistant, allowing the cancer to grow and spread. This is known as castration resistant prostate cancer (CRPC). There are two medications approved by the United States Food and Drug Administration for these cases, but patients see little or no long-term survival benefit with these therapies.
The androgen receptor (AR) remains the main driver of cancer growth in CRPC, eliminating its function remains essential. While these cancers have no additional mutations or other genetic overexpression, Penn's team was still able to identify a new target thanks to what the researchers called “AR co-pilot.”
“We know that AR does not work alone, it needs Med-1 as a partner, says the study's lead author, Irfan A. Asangani. Our study found a way to deactivate Med-1, leaving AR without its co-pilot, which means that cancer cannot grow and cells eventually die. ”
The use of an inhibitor to turn off CDK7 led to the death of CRPC cells both in the laboratory environment and in experimental models. The researchers also observed very limited effects outside the objective of this approach, since healthy cells have redundancies to deal with the loss of Med-1, which means that only cancer cells end up dying.
“Our theory is that these cancer cells are addicted to Med-1 and AR, but other cells are not, so we are essentially depriving them of their addiction,” says Asangani.
CDK7 inhibitors are already being tested in phase I clinical trials for other types of cancer, including leukemia, lung cancer, glioblastoma and breast cancer, but Asangani says this study shows the rationale for testing them in CRPC.