Research at UAMS Shows Potential to Reduce Chemo-related Heart Damage

Valentina Todorova, PhD

Results of a study led by UAMS cancer researcher Valentina Todorova, Ph.D., were published in the February 2020 issue of Translational Oncology.

| A team led by UAMS cancer researcher Valentina Todorova, Ph.D., has demonstrated the potential to prevent chemotherapy-induced heart damage without reducing the treatment’s effectiveness.

The study titled “Dantrolene Attenuates Cardiotoxicity of Doxorubicin Without Reducing its Antitumor Efficacy in a Breast Cancer Model” was published in the February 2020 issue of the scientific journal Translational Oncology.

Todorova’s team combined the muscle relaxant dantrolene with the chemotherapy drug doxorubicin to determine if it could help prevent heart damage — also called cardiotoxicity — without reducing the drug’s cancer-fighting ability.

“Cancer treatment can cause many side effects, including heart damage. In some patients, the damage appears during or soon after treatment. In others, it occurs many years later. We are looking at new ways to prevent this damage from occurring, specifically in breast cancer patients,” said Todorova, assistant professor in the UAMS College of Medicine Department of Internal Medicine.

Doxorubicin is commonly used alone or in combination with other drugs to treat many types of cancer, including breast cancer, Hodgkin and non-Hodgkin lymphoma, bladder cancer, stomach cancer and several others.

However, due to its well-documented and unpredictable side effects, doxorubicin’s usage can be limited.

“Heart damage caused by doxorubicin begins with the first round of chemotherapy and increases in severity based on the dosage the patient receives. Typically the damage starts as cardiomyopathy, which makes it harder for the heart to pump blood. This can then lead to congestive heart failure,” Todorova said.

Her research showed, for the first time, that dantrolene, when given in addition to doxorubicin, has the potential to prevent heart damage, without decreasing doxorubicin’s cancer-fighting ability.

Dantrolene is a muscle relaxant used to treat stiffness and spasms related to conditions such as stroke, spinal cord injury or multiple sclerosis.

“No one has previously studied this combination of drugs in cancer. Our preliminary study lays the foundation for further research, both by our team and others,” Todorova said.

Next steps for Todorova include examining the most effective dosage of dantrolene, how it is best delivered, and its effect on a tumor’s response or resistance to treatment.

This research was funded in part by the Arkansas Breast Cancer Research Project (ABCRP). Established in 1997 by the Arkansas General Assembly, the ABCRP funds research efforts into the cause, cure, treatment, early detection and prevention of breast cancer.

Additional UAMS authors on the paper are Eric R. Siegel, M.S., Department of Biostatistics; Yihong Kaufmann, Ph.D., Department of Surgery; Asangi Kumarapeli, M.D., Ph.D., Department of Pathology; Jeanne Y. Wei, M.D., Ph.D., Department of Geriatrics; Issam Makhoul, M.D., Department of Internal Medicine; and V. Suzanne Klimberg, M.D., Ph.D., and Aaron Owen, both formerly of UAMS.