Advanced Authentic Research

Comparative Analysis of the Effect of Doxorubicin on Breast Cancer Tumor Cells Versus Cardiomyocyte by Tia C. & Jocelyn L.

Summary

Doxorubicin (DOX) is one of the most effective chemotherapeutic drugs used against cancer. It works by preventing tumor cells from replicating through the inhibition of topoisomerase α (Top2α), an enzyme that regulates the coiling of DNA. However, it has been found that use of the drug has cardiotoxic side effects, increasing the risk of heart disorders such as severe dilated cardiomyopathy (DCM), the weakening of heart muscle in the left ventricle. DCM causes a reduction in the heart’s ability to pump blood efficiently, thus causing congestive heart failure among cancer patients who receive DOX during chemotherapy. Because congestive heart disease essentially hampers the ventricle’s ability to fill with or eject blood, the patient’s heart is severely weakened and its pumping efficiency is reduced. Among the 60% of pediatric cancer patients who receive DOX, 10% of them will develop DOX-induced cardiomyopathy (DIC) as a result up to fifteen years after they complete chemo. There is currently no pharmacological cure for DIC, leaving many of those afflicted with a heart transplant as their only option for treatment...Research on DIC using animal models is limited by inherent interspecies differences of reaction to DOX; using cancer patients currently going DOX treatment as human models is equally difficult due to their multi-drug treatments that would make it nearly impossible to isolate the effects of DOX alone, as well as the invasive procedures that would be necessary to extract cardiomyocytes from the heart. However, human induced pluripotent stem cell-induced-cardiomyocytes (hiPSC-CMs) have proved to be a valuable tool for modeling cardiovascular disease. Pioneered by Shinya Yamanaka in 2006, iPSCs are a type of stem cell that can be obtained by essentially transforming fully differentiated adult somatic cells into pluripotent stem cells through the introduction of four specific genes encoding for transcription factors. This technique has allowed researchers to generate in vitro functional, beating cardiomyocyte models to study the effects of DOX...