Protein discovery may prevent heart damage from cancer treatment

A recent study led by scientists at Washington State University has discovered that blocking a protein called CDK7 could help prevent heart damage caused by a widely used chemotherapy drug while also boosting the drug's effectiveness in killing cancer cells. This research, based on animal models, holds promise for developing future treatments that minimize the heart-related side effects of chemotherapy and improve overall cancer treatment outcomes.

The study, which was published in the journal Cardiovascular Research, focuses on doxorubicin, a chemotherapy medication commonly used for treating breast cancer, lymphoma, leukemia, and various other cancers. Despite its effectiveness in eliminating cancer cells, doxorubicin is known to be toxic to the heart, leading to potential long-term issues such as heart attacks, heart failure, and other cardiovascular diseases.

Doxorubicin remains an essential treatment for certain cancer types due to the lack of better alternatives. Senior study author Zhaokang Cheng, an associate professor at the WSU College of Pharmacy and Pharmaceutical Sciences, has been investigating the mechanisms behind doxorubicin-induced heart toxicity to make its use safer for cancer patients. Previous research by Cheng's team revealed that doxorubicin activates a protein known as CDK2, which in turn activates another protein called FOXO1, leading to heart cell death.

In collaboration with WSU cancer biology researcher Boyang (Jason) Wu, Cheng's team examined the role of another protein, CDK7, which is involved in cell growth and cancer development. The researchers found that CDK7 activates CDK2, setting off a chain of molecular signals that result in the death of heart cells. They also demonstrated that mice lacking the CDK7 gene were protected from the heart toxicity caused by doxorubicin.

To further explore this finding, the researchers used a CDK7 inhibitor drug called THZ1 to block the protein's activity. They assessed its impact on both heart health and cancer growth. Notably, similar CDK7 inhibitors are currently being tested as anticancer drugs in clinical trials, although their effects on the heart are not yet fully understood.

The research team found that using THZ1 not only improved heart function but also inhibited tumor growth in their animal models. According to Jingrui Chen, the study's first author and a WSU research associate, this dual benefit of enhancing heart health and reducing tumor size is a significant breakthrough.

Further research is needed to validate these findings. The researchers plan to test the effects of THZ1 on younger mice over a longer period to better simulate the long-term heart toxicity experienced by childhood cancer survivors treated with doxorubicin. Additionally, they aim to investigate other proteins that may be involved in the signaling pathway contributing to doxorubicin-related heart damage.

The study was primarily funded by the National Heart, Lung, and Blood Institute, a part of the National Institutes of Health, with additional support from the National Cancer Institute. The findings from this research could pave the way for new treatment strategies that not only safeguard the heart but also enhance the efficacy of chemotherapy, ultimately improving the quality of life and survival rates for cancer patients.