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A recent study circulation studied the mechanisms underlying the negative effects of chemotherapy for bad cancer on heart function.
Cardiovascular complications are the leading cause of morbidity and mortality among cancer survivors. These complications, including impaired cardiac function, are thought to be caused in part by cancer treatment.
Trastuzumab (Herceptin) and cardiac dysfunction
For example, trastuzumab, also called Herceptin, is an extremely effective chemotherapeutic agent used in bad cancer patients who possess the epidermal growth factor receptor 2 (HER2) protein. Trastuzumab, however, would have the most common cases of cardiac dysfunction in patients. It is therefore important to study the possible damaging effects on the heart of chemotherapy for bad cancer, as well as the effects of other anticancer drugs on overall heart health.
In a recent study published in circulationThe researchers used heart cells from healthy patient stem cells and bad cancer to study the mechanisms of trastuzumab-induced cardiac dysfunction. Specifically, they began by isolating and developing cardiac muscle cells from stem cells from 3 healthy participants and 7 patients with bad cancer.
Trastuzumab caused a less vigorous contraction of the cells
The administration of trastuzumab caused a less vigorous contraction of the cells of patients with bad cancer compared to cells from healthy participants. No differences were observed in cell death and in the structure of cellular components responsible for cardiac contraction.
These results are consistent with clinical findings, in which patients with HER + bad cancer have impaired heart contraction after treatment with trastuzumab. The authors believe that cardiac cells derived and developed from stem cells of bad cancer patients can be used as an effective model for studying the effects of chemotherapy on heart cells.
The researchers have also conducted other studies that have shown that trastuzumab works by disrupting the way cells consume energy. These results were validated by new experiments in which metformin, an FDA-approved drug for type 2 diabetes, caused by trastuzumab-depleted cells, was expected to contract more vigorously and absorb more glucose. In other words, improving the cell's ability to absorb glucose into energy has improved the contractile force of the cell.
Metformin may reverse the adverse effects of chemotherapy on the heart
In summary, the authors believe that the present study provides new information on the potential mechanisms by which trastuzumab can induce cardiac toxicity in bad cancer patients. In addition, they demonstrated that the use of metformin could be an effective strategy to eliminate the adverse effects of chemotherapy on the heart.
Further studies are needed
In the future, the authors plan to conduct a prospective study on the use of trastuzumab in patients with bad cancer to determine whether those who also take metformin for diabetes have a reduced number of cardiac side effects compared to those who do not take it.
If successful, the authors propose that clinicians can isolate the cells of patients with bad cancer with the help of trastuzumab and determine the risk of occurrence of cardiac dysfunction. These cells can furthermore be used to determine whether the patient would benefit from the use of metformin or other drugs to reduce the toxicity to the heart of the chemotherapeutic agents.
Written by Haisam Shah, BSc
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Reference: Kitani, T., Ong, S.G., Lam, C.K., Rhee, J.W., Zhang, J.Z., Oikonomopoulos, A., … and Witteles, R.M. (2019). Man-induced Pluripotent Stem Cell Model of Trastuzumab-induced Cardiac Dysfunction in Breast Cancer Patients. circulation.
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