Anthracycline Chemotherapy and Cardiotoxicity

Abstract

Anthracycline chemotherapy maintains a prominent role in treating many forms of cancer. Cardiotoxic side effects limit their dosing and improved cancer outcomes expose the cancer survivor to increased cardiovascular morbidity and mortality. The basic mechanisms of cardiotoxicity may involve direct pathways for reactive oxygen species generation and topoisomerase 2 as well as other indirect pathways. Cardioprotective treatments are few and those that have been examined include renin angiotensin system blockade, beta blockers, or the iron chelator dexrazoxane. New treatments exploiting the ErbB or other novel pro-survival pathways, such as conditioning, are on the cardioprotection horizon. Even in the forthcoming era of targeted cancer therapies, the substantial proportion of today’s anthracycline-treated cancer patients may become tomorrow’s cardiac patient.

Treatment for lymphoma and late cardiovascular disease risk: A systematic review and meta‐analysis

“…In general, treatment for lymphoma involves chemotherapy alone or in combination with radiation, stem cell transplantation, or biologic therapies . The long‐term cardio‐toxic effects of these treatments, especially chemotherapy regimens utilizing anthracyclines and radiation therapy, have become more apparent in cancer survivors over the past decade . We previously conducted a meta‐analysis and found that the number of deaths due to CVDs within HL and NHL survivors were 7.31 (95% CI, 5.29‐10.10) and 5.35 (95% CI, 2.55‐11.24) times greater than the general population, respectively .…”

Delivery of ROS Generating Anthraquinones Using Reduction‐Responsive Peptide‐Based Nanoparticles

“…One of the major chemotherapeutic compounds is the anthracycline doxorubicin (DOX) which is known for its beneficial therapeutic effects on multiple forms of cancer, but also causes serious side effects, notably significant cardiotoxicity. [ ][ ] One approach to reduce such side effects is through the use of nanosized drug delivery systems (DDS). Classic DDS are either composed of inorganic materials or made from self‐assembled soft matter .…”

“…Already used clinically, liposomal formulations of DOX have been shown to moderately reduce the cardiotoxic side effects associated with administering the free drug. [ ][ ][ ] …”

“…While the exact mechanism of anthracycline‐induced cytotoxicity is still unknown, the production of highly reactive free radicals and reactive oxygen species (ROS) is a generally accepted mechanism. [ ][ ][ ] It arises from the presence of a quinone moiety that can be readily reduced by cellular reductants to yield a semiquinone radical . In aerobic conditions, semiquinones can reduce molecular oxygen resulting in the formation of ROS, which can initiate radical chain reactions leading to oxidative stress and ultimately cellular death .…”

Editorial to: “Building a Bridge to the Future of Cardiovascular Drugs and Therapy”

“…It is increasingly evident that, despite the impressive benefits of emerging cancer therapies, a substantial proportion of today's successfully-treated cancer patients may become tomorrow's cardiac patient. The group of Prof Derek Yellon of the Hatter Cardiovascular Institute in London, reviews the mechanism of anthracycline cardiotoxicity, and potential methods being developed in order to protect against this injury [5]. This group also offer a review of the topic of cardioprotection in relation to exosomes, endogenous nanoparticles which had only recently been named at the time the Journal began, but which have seen a monumental explosion of interest in recent years [6].…”