Blocking a protein called CDK7 may stop heart damage caused by a widely used cancer chemotherapy drug, a recent study suggests. The researchers also discovered that inhibiting CDK7 could improve the drug’s ability to kill cancer cells. The study, which was conducted on animals, may lay the groundwork for future treatment approaches aimed at decreasing chemotherapy-related heart damage and boosting treatment efficacy. This could potentially extend the lives of cancer patients.
Blocking a protein known as CDK7 could prevent heart damage associated with a co <p>The study conducted by scientists at Washington State University found that a widely used cancer chemotherapy drug may be more effective when combined with a CDK7 inhibitor. The researchers discovered that inhibiting CDK7 could enhance the medication’s ability to kill cancer cells. The study, which was based on an animal model, suggests that this combination could potentially reduce chemotherapy-related heart toxicity and increase the effectiveness of treatment. This could have long-term benefits for cancer patients by potentially increasing their lifespan. Chemotherapy-related heart damage can manifest years after treatment and may lead to serious heart conditions such as heart attacks and heart failure.failure, cardiomyopathy, and various other forms of heart disease.” Published in the journal Cardiovascular Research, the WSU study honed in on doxorubicin, a chemotherapy drug utilized in the treatment of breast cancer, lymphoma, leukemia, and other types of cancer. Although capable of eliminating a wide range of cancer cells, doxorubicin and similar chemotherapy drugs are known for their heart toxicity. Despite this drawback, the drug continues to be widely used.
“Despite the heart toxicity, doxorubicin remains the primary treatment for certain types of cancer for which targeted therapies or alternative treatments are not available,” stated Zhaokang Cheng, senior author of the study.The WSU College of Pharmacy and Pharmaceutical Sciences professor, Cheng, is dedicated to understanding the causes of heart toxicity induced by the drug doxorubicin. By doing so, Cheng hopes to make the use of doxorubicin safer for patients who depend on it. This study is an extension of earlier research that found doxorubicin activates a protein called CDK2. This protein then triggers another protein, FOXO1, which leads to the death of heart cells. Cheng’s team worked with WSU cancer biology researcher Boyang (Jason) Wu to further investigate CDK7, a protein that supports cell growth and has been linked to the development of heart disease.The study looked at the connection between CDK7 and its role in heart cell death and cancer growth. The researchers discovered that CDK7 activates CDK2, which then triggers a series of molecular signals leading to heart cell death. They also found that mice lacking the CDK7 gene were protected from doxorubicin-induced heart toxicity. Using a CDK7 inhibitor called THZ1, they were able to block the protein’s activity and examine its impact on both heart health and cancer growth. While a similar inhibitor is currently being tested in clinical trials as an anticancer drug, its effects on the heart are not yet fully understood. The researchers emphasized that they are the first to study the effects of THZ1 on both the heart and tumor growth in the same model.WSU research associate Jingrui Chen stated that their study revealed that the CDK7 inhibitor drug has the potential to enhance heart function while also inhibiting tumor growth. The researchers noted that further research is necessary, but their findings indicate that combining doxorubicin and THZ1 could potentially reduce the risk of heart damage and improve the effectiveness of chemotherapy. The next phase of their research will involve studying the impact of THZ1 on heart damage and cancer growth in younger mice over a longer period of time, in order to more accurately reflect the long-term heart toxicity caused by doxorubicin in childhood cancer survivors.The researchers also intend to investigate other proteins that may play a role in the signaling pathway responsible for heart damage caused by doxorubicin. 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.
