Anthracyclines such as doxorubicin are highly effective chemotherapy agents used to treat many common malignancies. However, their use is limited by cardiotoxicity. In this video, , a cardiologist from Beth Israel Deaconess Hospital in Boston, explains that highly potent visnagin derivatives inhibit Cyp1 and prevent doxorubicin cardiotoxicity.
The following is a transcript of her remarks:
Anthracycline cardiotoxicity has been recognized now for decades, but we still don't have cardioprotective strategies that can be used either universally or even specifically in high-risk populations. Really, the mainstay of cardioprotection is an agent called dexrazoxane that, in practical terms, many oncologists hesitate to use because of the potential effects on the antitumor activity of doxorubicin.
This remains a big public health problem and specifically our laboratory has been trying to find new pathways that may contribute to cardiotoxicity that could be treated by specific cardioprotectants that could be used either in patients who are in the early stages of cardiotoxicity or in patients who are at high risk of developing cardiotoxicities due to the anthracycline treatment.
So our laboratory has been focused specifically on a pathway that we discovered in the zebrafish model where we give zebrafish doxorubicin and perform chemical screening, and we identified a class of compounds that appears to be very consistently and potently protective against the development of anthracycline cardiomyopathy.
Our current studies are focused on validating the efficacy of these compounds in both mouse models that more accurately recapitulate the human cardiomyopathy, as well as importantly, in human patients. So searching for biomarkers related to these new cytochrome P450 pathways may be useful in helping to risk-stratify patients as well as guide which patients may benefit from these types of cardioprotective strategies.