Medical staff from Stanford University Medical Center have posed two research questions in relation to cardiomyopathy (a form of congestive heart failure.) The first is why are heart muscle cells especially prone to damage from chemotherapy? The second question is why are only some cancer patients affected by this type of chemotherapy?
A further factor is the chemotherapy agent. Because of the range of different agents and the different physiological effects, the research study could only focus on one agent. A common chemotherapy drug called doxorubicin was selected. This drug is used for the treatment of leukemia, breast cancer, and multiple myeloma. Doxorubicin sold under the trade name Adriamycin.
As the basis for the research, scientists extracted skin cells from 12 women. Four of the women were cancer free; four had been diagnosed with breast cancer patients and who had experienced heart problems on receiving doxorubicin; and four were also diagnosed with breast cancer and were receiving doxorubicin, but they had not experienced any heart problems.
The extracted skin cells were ‘trans-morphed’ into induced pluripotent stem cells and then turned into heart muscle cells. The cells were studied for their response to doxorubicin, particularly rates of heart muscle cells death.
It was found that the patients identified as susceptible to doxorubicin had heart cells that entered into an irregular beating pattern and there was a higher rate of cell death. These differences were attributed to gene expression and that mitochondria, which hold cellular energy, are affected.
It is hoped the research will allow medical models to be developed to determine which patients are likely to be more susceptible to heart damage if they were to receive doxorubicin. This would allow for better care or for an alternative medication to be selected.
The research has been published in the journal Nature Medicine. The research is headed “Assessment of the effects of doxorubicin on DNA damage, calcium handling, and whole-cell oxidative stress in patient-specific hiPSC-CMs.”
